Pharmaceutical Wastes in Health Care Facilities

A hospital pharmacy can easily have thousands of distinct pharmaceutical chemicals in inventory. How should pharmaceuticals be managed when they can no longer be used by humans? Today we know that pharmaceuticals are found in our ground water. The common practice of flushing pharmaceuticals is no longer considered best practice, but the worst! Our task is to reduce occupational and environmental risks by safely managing and disposing of what we use, but to also develop a set up practices to use less in the first place and reduce the toxicity where alternatives exist.

Practice Greenhealth’s guide Managing Pharmaceutical Waste – A 10 Step Blueprint for Healthcare Facilities in the United States is the best place to start for a very comprehensive overview and recommendations for best practices.

Practice Greenhealth Workshop on Safe Pharmaceutical Disposal – May 15, 2007. Agendas and Presentations

Properties and Risks

The properties that make pharmaceuticals useful are the same properties that make them hazardous. Pharmaceutical substances are designed to affect human metabolism at very low concentrations—this potency does not necessarily change when a chemical enters the waste stream where an active ingredient in a discarded drug could act on an unintended target. The toxicity of pharmaceutical formulations can present both occupational and environmental hazards.

• Antineoplastic agents (the type of drug most often used in chemotherapy) are extremely toxic designed to kill dividing cells.

• Some radioactive compounds are used for the same purpose or are used as tracers or markers.

• Nitroglycerin causes blood vessels to dilate and can be used to treat chest pain, but it is also well known for its explosive properties. More

• Flammability hazards are common for drugs that use alcohol-water mixture for solubility so the drug can be administered in liquid form. These and other solvents can pose a fire hazard (ignitability)

• Preservatives and other ingredients can pose a toxicity hazard over and above the effect of the main active ingredient.

• 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)

TOOLS: NIOSH document – preventing workplace exposure to chemotherapeutic drugs. The index page provides a brief summary.

Compliance requirements

New Hampshire DES provides several detailed fact sheets on management and disposal of each type of listed and characteristic pharmaceutical waste.

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. For information on state requirements, consult the Practice Greenhealth Hazardous Waste State Locator

The screening procedure recommended here is an elaboration of the list provided on the Practice Greenhealth 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 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 pharmaceuticals that are being returned to the manufacturer for credit are not considered to be wastes, according to an EPA interpretation. (see below for more information on “reverse distribution”).

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

• Is it a listed waste on the RCRA:

• P-list?

• U-list?

• D-list?

• Is it a characteristic waste due to:

• toxicity?

• ignitability?

• corrosivity?

• reactivity?

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 circumstances such as wastes from cleanups?

Listed wastes

RCRA regulations provide several lists of materials that are automatically considered hazardous wastes. If the materials you are screening appears on these lists, your task is done – the waste must be handled as a hazardous waste. Refer to the Practice Greenhealth 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.

Practice Greenhealth has compiled tables listing materials in each of the RCRA P-, U-, and D- 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. (This selection is based a table appearing in an article by Charlotte Smith in the Journal of the Pharmacy Society of Wisconsin, November-December, 2002. The article contains much useful background information besides, and is recommended reading.)

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. (This link will take you to the most recent available version of 40 CFR 261.33.)

Common P-Listed Pharmaceuticals:

¹ 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:

² Chloral hydrate and paraldehyde are controlled substances regulated by the Drug Enforcement Administration and must be destroyed through a

“witnessed destruction process”. The article by Charlotte Smith cited above points out that “their status as a RCRA hazardous

waste makes disposal very difficult.”

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.

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

In addition to these brand names, your facility may contain various other listed drugs hat are used in cancer research or treatment, though they have not been FDA-approved for general use. Examples include:

• Azaserine U015

• Chlornaphazin U026

• Ethyl Carbamate U238

• 3-Methylchloranthrene U157

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:

• ignitability (D001)

• corrosivity (D002)

• reactivity (D003)

• toxicity (D0xx, where xx represents two digits from 04 through 43, and denotes a specific toxic chemical)

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

Ignitability

Examples of ignitable wastes include:

• flammable liquids (flash point less than 60^oC)

• 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: 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 aerosol propellants, it is necessary to go through the actual test procedure for measuring the flash point to make the determination. (It is a standard laboratory test.)

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 2) and bases (pH greater than 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.

Nitroglycerin is the only pharmaceutical that would fall under this definition (and is also a P-listed material). But healthcare facilities do not typically deal with the bulk form, and when packaged into individual doses, nitroglycerin is not explosive. According to a relatively recent (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.

More info:

• MN Pollution Control Agency document that clarifies the exemption and has the reference for the Federal Register notice. Note from MNTap – “that while finished dosage forms of nitroglycerin

are exempted from P listing, the waste must be evaluated for other hazardous waste characteristics, e.g. pH, and in MN, CA and WA, for lethality.

• Federal Register notice of the Rule change for “Mixture and Derived from Rule”.

Toxicity

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

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

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

Disposal of 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 usable pharmaceuticals can be returned to the manufacturer for credit. To facilitate this process, EPA has determined that healthcare facilities do not have to consider returned pharmaceuticals as “discarded materials”. This removes the burden of having to treat them as hazardous wastes (or, more properly, shifts the burden to the reverse distributor). In particular, facilities do not have to use a hazardous waste hauler or fill out manifests to ship returns, or to count returns in determining their hazardous waste generator status.

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. The Returns Industry Association (RIA) provides a list of members, who are, by RIA policy, “committed to high quality standards, economies within the reverse distribution process, full regulatory compliance, and protection of the environment”. RIA has also compiled a set of guidelines detailed the federal regulatory standards that apply to reverse distribution.

More resources

Practice Greenhealth’s Pharmaceuticals Guide—Managing Pharmaceutical Waste – A 10 Step Blueprint for Healthcare Facilities in the United States

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

• Evaluating pharmaceutical waste http://www.pca.state.mn.us/publications/w-hw4-45a.pdf

• Managing pharmaceutical waste http://www.pca.state.mn.us/publications/w-hw3-34.pdf (This also covers other general healthcare wastes.)

• Managing chemotherapeutics waste http://www.pca.state.mn.us/publications/w-hw4-03.pdf

• Florida Guide for pharmacies (1999, 24 pp) http://www.floridacenter.org/brochures_bulletins/rcra_pharmacies.pdf

• Washington State Department of Ecology pharmaceutical waste management resources – index page http://www.ecy.wa.gov/programs/hwtr/pharmaceuticals/index.html

• Includes pharmaceutical waste management flowchart

• King County (Seattle) has carried out an extensive survey characterizing the nature and quantity of pharmaceutical wastes from a variety of area healthcare facilities http://www.govlink.org/hazwaste/publications/PharmaceuticalWasteSurvey.pdf

Pharmaceutical Returns

• The Washington State DOE provides a good summary page on the returns industry.

Mercury-containing pharmaceutical products – The US Food and Drug Administration (FDA) list at http://www.fda.gov/cder/fdama/mercury300.htm

Articles:

• Charlotte Smith, Journal of the Pharmacy Society of Wisconsin, November-December, 2002) “http://www.ashp.org/practicemanager/PSW_article.pdf”: http://www.ashp.org/practicemanager/PSW_article.pdf

• Charlotte Smith, Health Facilities Management, January 2001, http://www.h2e-online.org/pubs/news/envsvcs.pdf

• Risk Management of Pharmaceuticals Entering POTWs and Municipal Landfills from Routine Hospital Waste Management Practices, Charlotte Smith

• Disposal of Hazardous Pharmaceutical Waste, M. Saljoughian, U.S. Pharmacist, 2004;6:HS-22-HS-24

Listen to Practice Greenhealth past teleconferences available on audio file.

• January 12, 2007 – Pharmaceutical Waste Management – Case Study – Abbott Northwestern Hospital, Minneapolis, MN

• May 12, 2006 – Pharmaceutical Waste – Learn Best Management Practices and How to be in Compliance with RCRA

H2E Workshop on Safe Pharmaceutical Disposal – May 15, 2007. Presentations