Friday, January 14, 2011

Pharmaceutical Wastes

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.
A few drugs have other properties, unrelated to their intended action, that makes them hazardous.  Nitroglycerin, for example, which causes blood vessels to dilate and can be used to treat chest pain, is also well known for its explosive properties.
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.

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 in often inherent in the function.  But the risks can be minimized and managed.

Compliance requirements
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 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 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. 
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 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-, 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:

Name No.
Arsenic trioxide
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:

Chloral Hydrate (CIV)2
Mitomycin C (chemo)
Chlorambucil (chemo)
Paraldehyde (CIV)2
Cyclophosphamide (chemo)
Daunomycin (chemo)
Selenium sulfide
Streptozotocin (chemo)
Lindane U129
Melphalan (chemo) U150
Uracil mustard (chemo)
Warfarin <0.3%
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.
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.
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 HERC Hazardous Waste Determination page for a general discussion of RCRA characteristic wastes.
Ignitability.  Examples of ignitable wastes include:
  • flammable liquids (flash point less than 60oC)
  • 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).
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).
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 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.
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:

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

Name No.
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

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.

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