Veterinary Compliance Assistance

Hazardous Pharmaceutical Waste

A veterinary pharmacy can easily have hundreds of 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 Spring/Summer 2022).


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 and animal 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. Insulin is included in this category.

A relevant property of pharmaceuticals unrelated to their function is their water solubility. 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 Hazardous Waste State Locator.

The screening procedure recommended here is an elaboration of the list provided on the VETCA 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 VetCA 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.

 VETCA 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.

Common P-Listed Pharmaceuticals:

Name No.
Arsenic trioxide P012
Dalfampridine (4-aminopyridine) P008
Epinephrine1 P042
Nicotine P075
Nitroglycerin2 P081
Physostigmine P204
Physostigmine salicylate P188
Warfarin >0.3% P001

1 Does not include epinephrine salts.

2 A federal exemption for nitroglycerin, in the form of finished dosages, was created in 2001, and has been adopted by some states.

Common U-Listed Pharmaceuticals:

Name No. Name No.
Chloral Hydrate (CIV)2 U034 Mitomycin C (chemo) U010
Chlorambucil (chemo) U035 Paraldehyde (CIV)2 U182
Chloroform U044 Phenacetin U187
Cyclophosphamide (chemo) U058 Phenol U188
Daunomycin (chemo) U059 Reserpine U200
Dichlorodifluromethane U075 Resorcinol U201
Diethylstilbestrol U089 Saccharin U202
Formaldehyde U122 Selenium sulfide U205
Hexachlorophene U132 Streptozotocin (chemo) U206
Lindane U129 Trichloromonofluromethane U121
Melphalan (chemo) U150 Uracil mustard (chemo) U237
Mercury U151 Warfarin <0.3% U248

2Chloral hydrate and paraldehyde are controlled substances regulated by the Drug Enforcement Administration and must be rendered "non-retrievable." DEA has currently only authorized incineration to ensure non-retrievability Subpart P exempts controlled substances from hazardous waste management IF they are destroyed by incineration at one of five types of incinerators.

Selected chemotherapy agents by brand name

Many of the chemicals used to treat cancer patients during chemotherapy fall on either the U or P lists. These agents are often referred to by their brand names rather than the chemical designations appearing on the lists. For your convenience, we have listed some common brand names below, together with their chemical names and RCRA waste codes.

Since new products may be introduced at any time, this list may not include all brand names composed of RCRA listed chemicals.

Brand name Chemical Name Code
Alkeran Melphalan U150
Cerubidine Daunomycin U059
CTX Cyclophosphamide U058
Cytotoxan Cyclophosphamide U058
Daunorubicin Daunomycin U059
DaunoXome Daunomycin U059
Leukeran Chlorambucil U035
Liposomal Daunorubicin Daunomycin U059
L-PAM Melphalan U150
Mitomycin Mitomycin C U010
Mutamycin Mitomycin C U010
Neosar Cyclophosphamide U058
Procytox Cyclophosphamide U058
Rubidomycin Daunomycin U059
Streptozocin Streptozotocin U206
Trisenox Arsenic Trioxide P012
Zanosar Streptozotocin U206

Note that while most chemotherapy agents are U-listed, arsenic trioxide is P-listed.

Other chemicals may be added to the RCRA lists at some point in the future. In any case, even if some of the chemotherapy agents in your facility are not currently included among the listed hazardous wastes, they are of necessity extremely toxic since their primary function is to kill dividing cells. You may want to consider handling all chemotherapy agents with the same level of care that is required for the listed hazardous wastes.

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 VetCA 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).

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

D-Listed Chemicals Found in Pharmaceuticals (with threshold levels):

Name No. Conc. (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

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 sent 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 status except 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:

AVMA Disposal of Unwanted Medications

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

VetCA Home