Pharmaceuticals - Hazardous Waste

A hospital pharmacy can easily have several thousand distinct pharmaceutical materials in inventory. Any of these materials can enter the waste stream, and some must be managed as hazardous wastes. This page will help you determine which rules apply. Please note that EPA's Final Rule: Management Standards for Hazardous Waste Pharmaceuticals and Amendment to the P-75 Listing for Nicotine, published on February 22, 2019 and in effect in federally managed states and territories on August 22, 2019, provides relief to healthcare facilities in many areas of pharmaceutical waste management but is stricter in others. Please refer to this EPA website for updated information on which states have adopted these regulations. Please refer to the upcoming Revised Blueprint for Managing Pharmaceutical Waste for detailed information on the Rule (Expected Fall 2021).


Properties

The properties that make pharmaceuticals useful are the same properties that make them hazardous. Pharmaceutical companies invest billions of dollars every year to develop substances able to affect human metabolism at very low concentrations. This potency does not change when a material enters the waste stream.

Some pharmaceuticals must be extremely toxic in order to function. Antineoplastic agents (the type of drug most often used in chemotherapy), for example, are designed to kill dividing cells. Some radioactive compounds are used for the same purpose.

Drugs in multidose vials have preservatives, such as thimerosal, which is mercury-based, or m-cresol, which causes the formulation to be classified as a hazardous waste. Multidose flu vaccine and insulin are included in this category.

A relevant property of pharmaceuticals unrelated to their function is their water solubility. In order to administer drugs in liquid form, those that are not sufficiently soluble in water must be dissolved in some kind of solvent, generally an alcohol-water mixture. This can pose a flammability hazard, as discussed below.


Risks

Pharmaceuticals in the waste stream can pose several different types of risk. The most straightforward is that the active ingredients in a discarded drug could act on an unintended target. But other ingredients in pharmaceutical formulations can present hazards:

  • Preservatives and other ingredients can pose a toxicity hazard over and above the effect of the main active ingredient
  • Some common solvents can pose a fire hazard (ignitability)
  • A few compounding agents are corrosive, including strong acids with pH less than 2 (such as glacial acetic and carbolic acids) and strong bases with pH greater than 12.5 (such as sodium hydroxide)
  • Some compounds are radioactive, including certain chemotherapy drugs, and certain agents that are used as tracers or markers.

Risks from pharmaceuticals in healthcare facilities generally cannot be eliminated by finding substitute materials, since the risk is often inherent in the function. But the risks can be minimized and managed.


Hazardous Determination

Your first task is to determine whether a given pharmaceutical waste material must be treated as a hazardous waste under RCRA. This section will help you through the federal regulations. Please note that other requirements may apply in your state, especially during this transitional time while Subpart P and Nicotine Exemption are being adopted state-by-state. For information on state requirements, consult the HERC Hazardous Waste State Locator.

The screening procedure recommended here is an elaboration of the list provided on the HERC Hazardous Waste Determination (HWD) page. We assume that you have already determined that the waste you are screening meets the definition of "solid waste", and that it is not excluded by a regulatory exemption. In general, these considerations are not likely to apply to pharmaceutical waste, but you may want to check the HWD page for more background information.

Note also that outdated pharmaceuticals that are being sent to a reverse distributor for credit, while considered to be a waste under EPA's Subpart P regulations, are allowed to be returned if they are "potentially creditable." (see below for more information on "reverse distribution").

The screening procedure consists of answering the following questions about the waste:

Note that nitroglycerin is the only drug that could be considered potentially reactive. Due to its very minute amount in drug formulations, it is exempt from regulation in final dosage forms under 40 CFR 261.3(g). This change enabled an exclusion of weak medicinal nitroglycerin from P081 listing since it never exhibits the characteristic of reactivity. The State of Connecticut does not accept this exemption.

In addition, the HWD page lists two additional questions that you should be aware of:

  • Is it mixed with a hazardous waste?
  • Is it derived from a hazardous waste?

Again, these considerations are less likely for pharmaceutical wastes, but may apply in some special circumstance

Listed wastes

RCRA regulations provide several lists of materials that are automatically considered hazardous wastes. If the materials you are screening appear on these lists, your task is done -- the waste must be handled as a hazardous waste. Refer to the HERC Hazardous Waste Determination page for background information on the RCRA lists.

However, there is one additional consideration. A peculiarity of the RCRA framework is that it treats mixtures differently from single substances. If the material in question is not the only active ingredient in the waste, you will need to apply different criteria. The mixture might still have to be treated as a hazardous waste if it has any of the hazardous waste characteristics (see below). If not, a 1988 determination from EPA appears to indicate that a formulation with more than one active ingredient might not fall within the RCRA definition of hazardous. This is yet another indication that the RCRA framework needs some serious work. Experts strongly recommend that in cases like this you treat these materials as if they were RCRA hazardous wastes, if only as a matter of common sense.

HERC has compiled tables listing materials in each of the RCRA P- and U- lists which may typically be found in healthcare facility waste streams together with their typical uses. For your convenience, a selection from the list covering pharmaceuticals specifically is reproduced below

Please note that these lists are not intended to be complete. The full lists of all P- and U-listed wastes appear in the Code of Federal Regulations, 40 CFR 261.33.

Examples of the Most Common P- and U-Listed Drugs

Name of Drug

Medical Use

Hazardous
Waste Code

Arsenic trioxide

Antineoplastic

P012

Dalfampridine (4-aminopyridine)

Multiple sclerosis

P008

Nicotine

Replacement therapy

P075

Physostigmine salicylate

Glaucoma

P188

Warfarin >0.3%

Blood thinner

P001

Chloral hydrate (CIV)

Sedative

U034

Cyclophosphamide

Antineoplastic

U058

Daunomycin

Antineoplastic

U059

Lindane

Lice, scabies

U129

Melphalan

Antineoplastic

U150

Mitomycin C

Antineoplastic

U010

Selenium sulfide

Anti-fungal, dandruff

U205

Streptozotocin

Antineoplastic

U206

While there are only six antineoplastic chemotherapy drugs on the P- and U-lists that are currently on the market, many more highly toxic drugs have been introduced into the market since 1980 when the lists were published. In the National Institute of Occupational Safety and Health (NIOSH) Hazardous Drug List 2020, these and other antineoplastic chemotherapy drugs are listed in the NIOSH Table One and the healthcare industry routinely manages these as a hazardous waste as a best practice. In addition, the paraphernalia associated with these drugs, such as empty vials, syringes, wipes, gloves, and gowns, are typically segregated into a waste stream commonly called "trace chemotherapy waste" and disposed of as regulated medical waste and incinerated at hazardous waste or medical waste incinerators (regulated as HMIWIs (hospital, medical and infectious waste incinerators)).

Characteristic Wastes

Making explicit lists is a good way to ensure that specific materials are covered under the RCRA rules. But there are more potentially dangerous materials in existence than any practical list could possibly contain. So RCRA provides another way for a material to qualify as hazardous. Four characteristics, or material properties, have been singled out as posing a particular risk of damage to people or the environment. They are:

Each of these topics is related specifically to pharmaceutical wastes in the discussion below. See the HERC Hazardous Waste Determination page for a general discussion of RCRA characteristic wastes.

Ignitability

Ignitability. Examples of ignitable wastes include:

  • flammable liquids (flash point less than 60°C)
  • solids that can start burning through friction or absorption of moisture
  • certain compressed gases

For pharmaceuticals, the presence of a flammable solvent is the most typical reason that a particular formulation must be considered ignitable. Mixtures of alcohol and water are often used in pharmaceutical formulations. As it turns out, there is a special provision written into the RCRA definition of ignitability, called the "alcohol exclusion" that sets a threshold of 24% alcohol as a lower limit. That makes the determination easy for alcohol-water mixtures where the water is 50% or more of the ingredients: if it contains more than 24% alcohol, it should be considered an ignitable hazardous waste. For other flammable materials present in pharmaceutical formulations, such as some aerosol propellants, it is necessary to determine the flash point which should be provided on the product's SDS (Safety Data Sheet).

There are also a few strong oxidizers used in pharmaceuticals formulations. Examples include silver nitrate and potassium permanganate.

The regulations covering the ignitability characteristic can be found in Title 40 of the Code of Federal Regulations, Part 261, Section 21 (40 CFR 261.21).

Name of Drug

Dosage Form

Medical Use

Reason

Paclitaxel Injection

Vial

Antineoplastic chemotherapy

Alcohol 49.7%

Aromatic Ammonia Inhalant

Ampule


Alcohol 35%

Cleocin-T Topical Solution 1%

External Liquid

Antibiotic

Isopropyl Alcohol 50%

Compound W Gel 17% Salicylic Acid

Gel

Wart Remover

Alcohol 60%+

Minoxidil Solution

External Liquid

Hair Growth Stimulant

Alcohol >24%

Nitroglycerin Injection 5 mg/ml

Vial

Angina

Alcohol 30%

Tretinoin Gel 0.025%

Gel

Acne

Denatured Alcohol 83%

Testosterone Gel CIII

Gel

Replacement Therapy

Alcohol 74%  (also a DEA controlled substance)

Swimmer’s Ear Drops

External Liquid

Ear Infection

Isopropyl Alcohol 95%

Corrosivity

This RCRA category refers to strong acids (pH less than or equal to 2) and bases (pH greater than or equal to 12.5).

Only a few examples of this type of waste are likely to be found associated with pharmaceuticals. Glacial acetic acid and concentrated sodium hydroxide may sometimes be used in compounding off-the-shelf pharmaceuticals for custom uses. Either of these materials would be considered as corrosive hazardous wastes.

The regulations covering the corrosivity characteristic can be found in Title 40 of the Code of Federal Regulations, Part 261, Section 22 (40 CFR 261.22).

Reactivity

A waste is reactive in the RCRA sense if it is liable to explode, or to react violently or release toxic gases if it comes in contact with water.

The only pharmaceutical that would fall under this definition is nitroglycerin (which is also a P-listed material). But healthcare facilities do not deal with the bulk form, and when diluted for medicinal use, nitroglycerin is not explosive. According to a 2001 ruling by the EPA, if a waste contains a P or U listed material in a form in which it does not exhibit its characteristic property, it does not have to be regarded as hazardous. Nitroglycerin in dosage form falls under this ruling, and thus does not have to be treated as hazardous.

Toxicity

See the HERC Hazardous Waste Determination page for the RCRA definition of toxicity. The following table includes the D-listed chemicals most commonly associated with pharmaceuticals:

Toxicity Characteristic Constituents Found in Drug Formulations

Name of Toxicity Characteristic Constituent

Hazardous Waste Code

Max Regulatory Level (mg/L)

Common Drug Formulations

Arsenic

D004

5.0

Arsenic trioxide injection

Barium

D005

100.0

Entrobar® Suspension

Chloroform

D022

6.0

Chloroform

Chromium

D007

5.0

M.T.E.-5® Concentrate

M-Cresol

D024

200.0

Humalog® Injection 100 units/ml

Lindane

D013

0.4

Lindane Lotion

Mercury

D009

0.2

Multi-dose Flu Vaccine (Thimerosal)

This link will take you to the most recent available version of the complete D-list.


Disposal of hazardous pharmaceutical wastes

The best pollution prevention alternative, elimination or substitution of hazardous materials, is typically not an option for pharmaceuticals, since their hazards and their functionality are two sides of the same coin.

But for pharmaceuticals, there is an alternative that is not available for most other hazardous substances. "Reverse distribution" is a process whereby some unused, but potentially creditable pharmaceuticals can be send to a reverse distributor for credit. Under Subpart P, outdated pharmaceuticals are considered to be a waste at the healthcare facility. If they meet the criteria of "potentially creditable," they may be shipped to a reverse distributor for credit evaluation. To be potentially creditable, the drug must be in the original manufacturer's container, in-date or within one year of the expiration date, and not dispensed to a patient. Facilities do not have to use a hazardous waste hauler or fill out manifests to ship returns but must obtain and keep documentation of the shipment and receipt by the reverse distributor for 3 years. As with all other hazardous waste pharmaceuticals under Subpart P, these will not country towards determining their hazardous waste generator statusexcept for the initial determination after their state adopts Subpart P.

It is important to recognize that the exclusion applies only to bona fide returns for credit, and not to broken containers, spilled contents, compounding leftovers, or similar cases. It is also important to deal with reverse distributors who are themselves in compliance.


More resources

Articles:

The Minnesota Pollution Control Agency provides several useful factsheets, with links to additional resources:

Other websites with useful information regarding hazardous waste pharmaceuticals, including waste reduction strategies:

HERC – Pharmaceuticals Waste Reduction

EPA - Management of Hazardous Waste Pharmaceuticals

Wisconsin DNR: Non-Household Pharmaceutical Waste

Minnesota Technical Assistance Program pollution prevention for healthcare

US DOJ DEA Drug Disposal Information

©2015 Healthcare Environmental Resource Center
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