Journal of the Pharmacy Society of Wisconsin Nov/Dec 2002 17

Feature

hile not everyone considers the development of knowledge and systems to properly manage pharmaceutical

waste to be an inherently glamorous field of study, we can all

relate to how important it is have our household waste managed. A strike by city environmental services personnel or a

backed up sewer system suddenly becomes a major priority for

our health and wellbeing.

The disposal of waste pharmaceuticals has been a much

more subtle, but no less important, issue. For many years,

pharmacists have been primarily concerned with ensuring that

wasted drugs were rendered unrecoverable through sewering

or incinerating. The focus was on insuring that children did not

gain access or that illegal diversion did not occur.

Not too much has changed, except that hospital incinerators

are a thing of the past and more waste pharmaceuticals are now

being disposed of in biohazardous1 sharps containers, in lieu

of a dedicated pharmaceutical waste stream. Sewering remains

a common choice.

So why should we be concerned about this historically

rather simple process? Unfortunately, since pharmacists do

not routinely receive instruction in environmental regulations,

by Charlotte A. Smith, RPh, MS

MANAGING

PHARMACEUTICAL

WASTE

we have been largely unaware of a large body of law: the

federal Resource Conservation and Recovery Act, enforced by

the Environmental Protection Agency and authorized states,

which regulates the disposal of solid waste in the United States.

EPA and hazardous chemical waste

In addition to defining “solid waste,” which includes liquids and gases, RCRA (pronounced rec-rah) also defines

hazardous waste — those chemicals or formulations deemed to

be so detrimental to the environment that they must be segregated for special waste management and cannot be sewered or

landfilled. A number of drug entities and pharmaceutical

formulations meet the definition of hazardous waste, including

such common drugs as epinephrine, nitroglycerin, warfarin,

nicotine, and seven common chemotherapy agents.

Endocrine disruptors

As if violating the law weren’t enough to get our attention,

being a generally law-abiding group of professionals, there are

other compelling reasons to take a hard look at the final resting

place of any drug waste we generate. Growing evidence

indicates that “endocrine disruptors,” — those chemicals that

mimic natural hormones, trigger an identical response, or

block natural hormones — are having a dramatic negative impact on

critical developmental stages in the

fetus and newborn. The book Our

Stolen Future2 documents the research of pharmacist, Theo Colburn,

who identified this phenomenon

among wildlife populations. In addition to the obvious impacts

of the estradiols, testosterone and progesterone related drugs,

pesticides such as lindane (an estrogen mimic) can cause

significant damage if they enter the environment inappropriately. Lindane was recently banned for all use, both human and

pesticide, in California and Canada.

With human male sperm counts dropping 50%3 on average

world-wide since 1939, an increase in infertility, genital deformities, hormonally triggered cancers such as breast cancer and

prostate cancer, and an upswing in neurological disorders in

children, we have an even greater responsibility as health care

professionals to ensure that our activities as pharmacists “do

no harm” through inadvertent secondary exposure.

Pharmaceuticals in surface waters

In March of 2002, the United States Geological Society

released the results of the first nationwide reconnaissance of

the occurrence of pharmaceuticals, hormones and other organic wastewater contaminants (OWCs) in surface waters.4

USGS surveyed 139 streams across the country, including

three in Wisconsin, looking for 95 different OWCs. One or

more contaminants was found in 80% of the samples, and

What Pharmacists Should Know
18 Nov/Dec 2002 Journal of the Pharmacy Society of Wisconsin

included common pharmaceuticals.

Water treatment plants to date are designed to filter out sediment, bacteria

and viruses. They have not in the past

been designed to identify and remove

organic molecules.

How do we generate

pharmaceutical waste?

In the past, much of the pharmaceutical waste occurring at a pharmacy was

due to expired pharmaceuticals. The

development of reverse distribution

companies has enabled pharmacies to

ship all outdated drugs as products back

through these firms for the purpose of

returning them to the manufacturer for

credit. Any outdated items that do not

meet the manufacturers’ return policy

become waste at the reverse distributor

which becomes the waste generator,

since this is where the decision to discard the item is made. This practice has been supported by the

EPA through two guidance letters to the industry.5 ,6 The letters

make it clear, however, that while EPA will consider an

outdated drug to remain a product until the decision is made to

discard it, reverse distribution cannot be used solely as a waste

management tool. Obviously wastelike materials, such as

partial vials, compounded IVs, and broken or spilled materials,

must be considered waste at the pharmacy and managed in

compliance with RCRA.

Other sources of pharmaceutical waste include undispensed

compounded products, discontinued indated items, unused

unit dosed items, unused IVs, and patients’ personal medications.

The Resource Conservation and Recovery Act

Enacted in 1976 as a response to national environmental

disasters, the purpose of RCRA is to encourage waste minimization, define hazardous waste, and provide for a system of

“cradle to grave” tracking of hazardous waste. Since the word

“hazardous” is used in multiple contexts within health care, it

is important to recognize that we are not talking about

biohazardous, infectious waste, OSHA hazardous materials as

featured in employee Right to Know programs, or DOT hazardous substances. EPA has an entirely different set of criteria for

defining hazardous chemical waste as it impacts human health

and the environment when discarded.

In case the compelling evidence surrounding species viability is not sufficient to encourage compliance, EPA has

provided for more prosaic motivators, such as personal and

corporate liability. Corporate fines may be levied at a rate of

$27,500 per violation per day and responsibility extends from

the manager level up through the CEO of the organization.

Personal liability carries no statute of limitations and, in

criminal cases of knowing, willful violation, can involve

prison sentences.

Waste generation status

If an organization generates hazardous waste, it falls into one

of three categories, based on the amount generated per month:

1. Conditionally Exempt Small Quantity7

2. Small Quantity

3. Large Quantity

Small and large quantity generators8 must notify EPA of

their generation activities and receive an EPA identification

number which remains with the physical site regardless of

change in ownership or operation. The caveat which boosts

pharmacy waste generation into large quantity status is the

generation of more than 1 Kg. (2.2 lbs) of P-listed waste in a

calendar month. Which leads to the question, which drugs

become hazardous waste when discarded?

Defining hazardous pharmaceutical waste

Applying RCRA to waste pharmaceuticals, we find the

following definitions:

 The P list9

 The U list10

 The four characteristics of hazardous waste

• ignitability11

• toxicity12

• corrosivity13

• reactivity.14

 

 

 

 

 

 

Managing Pharmaceutical Waste

Diagram 1
Journal of the Pharmacy Society of Wisconsin Nov/Dec 2002 19

P-listed chemicals are considered

“acutely hazardous” by EPA — the

worst of the worst. If a chemical on the

P list is the sole active ingredient of a

discarded product, it causes the entire

product, including the solvent and container, to be contaminated and must be

treated as a hazardous waste. Pharmaceuticals on the P list include:

 arsenic trioxide (P012)

 epinephrine (P042)

 nicotine (P075)

 nitroglycerin (P081)

 physostigmine (P204)

 physostigmine salicylate (P188)

 warfarin over 0.3% (common

dosage forms) (P001)

U-listed chemicals include a broader

range of pharmaceuticals and again must

be the sole active ingredient to come

under regulation. From the scientific

perspective of a pharmacist, the sole

active ingredient criterion is suspect. For example, the topical

anesthetics Fluori-Methane® and Aerofreeze® both contain

two U-listed chemicals, dichlorodifluoromethane and

trichloromonofluoromethane. Technically, these items would

not be regulated as hazardous waste when discarded since

neither U-listed ingredient is the sole active ingredient. Common sense and professional knowledge, however, should lead

us to manage these as hazardous wastes.

This same lack of rationality plagues the regulation in the

case of chemotherapeutic agents. The P and U lists have not

been updated substantially since 1976, when only the seven

chemotherapy agents in use at the time were U-listed:

 chlorambucil (U035)

 cyclophosphamide (U058)

 daunomycin (U059)

 melphalan (U150)

 mitomycin C (U010)

 streptozotocin (U206)

 uracil mustard (U237)

Our professional knowledge of the toxicity of chemotherapeutic agents should encourage us to manage all bulk and

residue chemotherapy agents as chemical hazardous waste.

See Table 1 for a complete list of pharmaceuticals that are Pand U-listed.

Chemotherapy waste vs. hazardous waste

Before we proceed to the description of the four characteristics of hazardous waste, it is very important to distinguish

between what the industry terms “chemowaste” and RCRA

Managing Pharmaceutical Waste

hazardous waste. Currently, medical waste disposal firms

offer a waste stream for chemotherapy waste. They accept

empty15 vials, syringes, and IVs, plus other paraphernalia,

such as tubing, gowns and gloves that contain trace amounts of

chemotherapy agents. Unbeknownst to most pharmacists, this

waste stream is managed as biohazardous, infectious waste. At

best, it is incinerated in a medical waste incinerator. At worst,

it is microwaved or autoclaved, then shredded and landfilled.

None of these processes ensures the destruction of the organic

molecules and their proper final disposition. Bulk and residue

chemotherapy agents should be segregated into containers

labeled RCRA Toxic Hazardous Waste along with other P- and

U-listed waste and D-listed wastes we’ll address below.

Characteristics of hazardous waste

The EPA defines four characteristics of hazardous waste:

 ignitability (D001)

 toxicity (D number specific to the chemical)

 corrosivity (D002)

 reactivity (D003)

Ignitability has a great impact on pharmaceuticals since

any aqueous formulation containing 24% or more alcohol is

ignitable under this definition. In addition, a nonaqueous

solution such as flexible collodion meets the flashpoint definition of less than 140o F. Oxidizers such as silver nitrate and

potassium permanganate and aerosols with flammable propellants also qualify.

Toxicity is by far the most difficult characteristic to identify. The good news is that, of about 40 chemicals listed by

Diagram 2
20 Nov/Dec 2002 Journal of the Pharmacy Society of Wisconsin

EPA, only ten of them apply to pharmaceuticals and only in

concentration levels above a certain regulatory limit (See

Table 2 Toxicity Characteristic Regulatory Limits). The bad

news is that the waste generator is responsible for determining

if their waste meets that criteria and the exit levels are different

for each chemical. For example, mercury, which is D009, has

an exit level of less than .2mg/Liter causing any preparation

containing a mercury preservative to come under regulation as

a hazardous waste. Vaccines and topical eye and ear preparations often contain mercury and must therefore be discarded as

hazardous waste.

Corrosivity is much easier to manage, since it involves very

acidic (pH < or + to 2) or very basic (pH> or = to 12.5)

chemicals. Normally these would only be found in the compounding area. The simplest way to manage these chemicals is

to review the compounding area annually and contract with a

hazardous waste broker to properly package and manage any

discarded items.

The final characteristic, that of reactivity, is interesting in

that the only relevant chemical is nitroglycerin. It is also Plisted, making it significant. Fortunately, the EPA recently

exempted dosage forms of nitroglycerin from federal regulation.16 ,17 Because the Wisconsin Department of Natural Resources has mirroring regulations at the state level, an exemption must also be granted by the WDNR before waste

nitroglycerin dosage forms can be removed from hazardous

waste management by Wisconsin pharmacies and health care

facilities. Even then, if the waste is being transported to a state

which has not exempted it, nitroglycerin may need to remain

a hazardous waste.

How should hazardous waste

be managed?

If we consider common pharmaceutical waste streams, we can usually identify five basic types: municipal waste,

sewer system, chemo-waste sharps,

chemo-waste soft, and red sharps. Noninfectious sharps may also be segregated. Note in Diagram 1, Common

Pharmaceutical Waste Streams, that it

is not unusual for controlled substances

and antibiotics to be sewered, along

with other IV fluids such as D5W and

NaCl.

To properly manage RCRA hazardous waste, we need to establish at least

two other waste streams: toxic hazardous waste and ignitable hazardous waste

(Diagram 2, Recommended Additional

Pharmaceutical Waste Streams). Based

on the medical waste vendor being used,

the pharmacy may also need to segregate and identify nonhazardous pharmaceutical waste. Medical waste vendors are NOT permitted to accept RCRA hazardous waste and are becoming much more cautious when accepting

any waste pharmaceuticals to prevent violations in their acceptance procedures.

A new schema of pharmaceutical waste management would

therefore include these three additions, with P-, U- and Dlisted wastes, bulk and residue chemotherapy and chemo spill

clean-up materials being placed into the toxic hazardous waste

containers. (See Diagram 3, Recommended Pharmaceutical

Waste Streams.) Those items meeting the criteria for ignitable

hazardous waste would be segregated into the Ignitable Hazardous Waste containers. These containers would be properly

labeled, stored, manifested, transported and disposed of by a

hazardous waste broker and a federally permitted RCRA

incineration firm. The management of these wastes at the

pharmacy or health care facility can be accomplished either by

internal expertise, if available, or through commercial hazardous waste brokers.

Nonhazardous waste pharmaceuticals may be segregated

and could potentially continue to be disposed of by the current

medical waste disposal firm, based on their permits.

How do we make this happen?

The profession of pharmacy is looking at a new system for

identifying and managing this newly recognized waste stream.

Therefore, new tools and resources must be developed to assist

pharmacies in making this transition in a cost-effective manner. To address the need for hazardous waste containment

 

 

 

 

 

 

 

Managing Pharmaceutical Waste

Diagram 3
Journal of the Pharmacy Society of Wisconsin Nov/Dec 2002 21

Managing Pharmaceutical Waste

Table 2. D List of Chemicals*

Hazardous Regulatory

Name Waste No. Level (mg/L)

Arsenic D004 5.0

Barium D005 100.0

Cadmium D006 1.0

Chloroform D022 6.0

Chromium D007 5.0

M-Cresol D024 200.0

Lindane D013 0.4

Mercury D009 0.2

Selenium D010 1.0

Silver D011 5.0

* D List of Chemicals Present in Pharmaceuticals that Cause a Waste to

Exhibit the Toxicity Characteristic When Present at or above the Maximum

Concentration or Regulatory Level. Note: For a complete listing of all 40

chemicals and their regulatory limits, see Section 4, 40 CFR 261.24 Toxicity

Characteristic. Available at: http://www.access.gpo.gov/nara/cfr/cfrhtml_00/

Title_40/40cfr261_00.html Accessed August, 2002.

Table 1. P- and U-Listed Pharmaceuticals

Hazardous

Name Waste Number

Arsenic trioxide P012

Epinephrine P042

Nicotine P075

Nitroglycerin1 P081

Physostigmine P204

Physostigmine salicylate P188

Warfarin >0.3% P001

Chloral Hydrate (CIV)2 U034

Chlorambucil (chemo) U035

Chloroform U044

Cyclophosphamide (chemo) U058

Daunomycin (chemo) U059

Dichlorodifluromethane U075

Diethylstilbestrol U089

Formaldehyde U122

Hazardous

Name Waste Number

Hexachlorophene U132

Lindane U129

Melphalan (chemo) U150

Mercury U151

Mitomycin C (chemo) U010

Paraldehyde (CIV) U182

Phenacetin U187

Phenol U188

Reserpine U200

Resorcinol U201

Saccharin U202

Selenium sulfide U205

Streptozotocin (chemo) U206

Trichloromonofluromethane U121

Uracil mustard (chemo) U237

Warfarin <0.3% U248

NOTE: This is not a comprehensive list of P and U listed chemicals. For a

complete list, refer to Section 4, 40 CFR Section 261.33 Discarded commercial chemical products, off-specification species, container residues and spill

residues. Available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/

Title_40/40cfr261_00.html Accessed September, 2002.

1 Nitroglycerin in finished dosage forms has been exempted federally based

on a Federal Register Notice dated May 16, 2001 (Volume 66, Number

95)(Page 27266-27297). Since every state except Iowa and Alaska have

mirroring regulations, check with the Wisconsin Department of Natural

Resources to determine the status of waste nitroglycerin dosage forms in

Wisconsin.

2 Chloral hydrate and paraldehyde are controlled substances regulated by the

Drug Enforcement Administration in schedule IV as an indication of moderate abuse potential. Since controlled substances must be destroyed through a

witnessed destruction process, their status as a RCRA hazardous waste makes

disposal very difficult.

Charlotte A. Smith is President of

PharmEcology® Associates, LLC in

Brookfield, WI. For more information, contact

Ms. Smith at 262-814-2635 or

csmith@pharmecology.org.

continued . . .

geared to the pharmacy and health care environment, the

SharpsSafety Division of the Kendall® Healthcare Company

is currently working with PharmEcology® Associates, LLC to

develop EPA and DOT compliant collection containers and

appropriate labels. To address the need for a simple method of

identifying which waste pharmaceuticals are hazardous waste

under RCRA, PharmEcology® Associates, LLC is currently

developing a subscription web-based search engine that will

enable subscribers to enter the National Drug Code, brand or

generic name of any drug product on the market and determine

if it is a hazardous waste.

Summary

Regulatory pressure and environmental concerns are causing pharmacists to take a new look at how waste pharmaceuticals are being managed by their organizations. The EPA’s

Resource Conservation and Recovery Act defines hazardous

chemical waste, which applies to a number of common pharmaceuticals when they are discarded. Each organization needs

to evaluate which of the pharmaceuticals it discards meet the

three criteria of hazardous waste: P-listed, U-listed or characteristic waste. These items must be segregated into the appropriate waste stream and managed as hazardous waste, utilizing

either internal expertise or a hazardous waste broker. ■

References

1. The term “biohazardous” refers to infectious medical waste and is disposed of in either red sharps containers or red bags by a regulated medical

waste disposal firm. Pharmacy as a profession has sometimes referred to

any item which may be hazardous to living systems as “biohazardous,”

which is a misnomer and confusing to other health care professionals.

2. Colborn, Theo; Dumanoski, Dianne; Peterson Myers, John. Our Stolen

Future, Plume Printing, March, 1997. Available at: http://

www.ourstolenfuture.org/#. Accessed September, 2002.

3. Ibid. p.9.

4. Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999-2000: A National Reconnaissance”; Environmental Science & Technology, V. 36, no. 6, pages 1202-1211. Available

at: http://pubs.acs.org/journals/esthag/36/i06/pdf/es011055j.pdf. Accessed

September, 2002.

5. Corson, A., Chief, Waste Characterization Branch, Hazardous and Industrial Waste Division, Office of Solid Waste, USEPA. Letter to Steven

Wittmer, Merck Sharp and Dohme, May 13, 1981. Available at: http://

yosemite.epa.gov/osw/rcra.nsf/5a8fdb3a65478a6b852565de00520ec3/

f3001b817ef4265885256611005156d2?OpenDocument Accessed September, 2002.

6. Lowrance, S., Director, Office of Solid Waste, USEPA. Letter to Mark

Schulz, Pharmaceutical Services, Inc., Browning Ferris Industries, May

16, 1991. Available at: http://yosemite.epa.gov/osw/rcra.nsf/
22 Nov/Dec 2002 Journal of the Pharmacy Society of Wisconsin

Managing Pharmaceutical Waste continued . . .

5a8fdb3a65478a6b852565de00520ec3/

354fe6a290ed95e1852565da006f04a1?OpenDocument Accessed

September, 2002.

7. 40 CFR PART 261—IDENTIFICATION AND LISTING OF

HAZARDOUS WASTE 261.5 Special requirements for hazardous

waste generated by conditionally exempt small quantity generators.

Available at: http://www.access.gpo.gov/nara/cfr/cfrhtml_00/

Title_40/40cfr261_00.html Accessed September, 2002.

8. 40 CFR PART 262—STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Available at: http://

www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr262_00.html Accessed September, 2002.

9. 40 CFR § 261.33 Discarded commercial chemical products, offspecification species, container residues, and spill residues thereof.

Available at: http://www.access.gpo.gov/nara/cfr/cfrhtml_00/

Title_40/40cfr261_00.html Accessed September, 2002.

10. Ibid.

11. 40 CFR § 261.21 Characteristic of ignitability. Available at:

http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr261_00.html Accessed September, 2002.

12. 40 CFR § 261.24 Toxicity characteristic. Available at: http://

www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr261_00.html Accessed September, 2002.

13. 40 CFR § 261.22 Characteristic of corrosivity. Available at:

http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr261_00.html Accessed September, 2002.

14. 40 CFR § 261.23 Characteristic of reactivity. Available at:

http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr261_00.html Accessed September, 2002.

15. There is a misconception in the pharmaceutical industry that

3ml of residue is allowable. This is due to a misreading of the

regulations, which state that first, all contents that can be removed

by normal means, including aspirating, have been removed. Then,

a 3% residue is allowable to accommodate residual drainage from

large containers, such as 55 gallon drums. 40 CFR § 261.7 Residues of hazardous waste in empty containers. Available at: http://

www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/

40cfr261_00.html Accessed September, 2002.

16. USEPA Federal Register Environmental Document, Hazardous

Waste Identification Rule (HWIR): Identification and Listing of

Hazardous Waste. [Federal Register: November 19, 1999 (Volume

64, Number 223)] [Proposed Rules][Page 63381-63461]From the

Federal Register Online via GPO Access

[wais.access.gpo.gov][DOCID:fr19no99-35] [[Page 63381]]Available at: http://www.epa.gov/fedrgstr/EPA-WASTE/1999/November/Day-19/f29067.htm Accessed September, 2002.

17. USEPA Federal Register Environmental Document, Hazardous

Waste Identification Rule (HWIR):Revisions to the Mixture and

Derived-From Rules AGENCY: Environmental Protection Agency

(EPA). ACTION: Final rule. [Federal Register: May 16, 2001

(Volume 66, Number 95)][Rules and Regulations][Page 27266-

27297] From the Federal Register Online via GPO Access

[wais.access.gpo.gov][DOCID:fr16my01-23] Available at: http://

www.epa.gov/fedrgstr/EPA-WASTE/2001/May/Day-16/

f11411.htm Accessed September, 2002.