The Core Definition: NIOSH Criteria for a Hazardous Drug
The National Institute for Occupational Safety and Health (NIOSH) is the primary authority in the United States for identifying which drugs are hazardous [1.2.2, 1.3.3]. The determination is not based on the drug's therapeutic effect for a patient, but on the occupational risk it poses to healthcare workers during its entire lifecycle—from manufacturing and transport to administration and disposal [1.3.2, 1.5.2].
A drug is classified as hazardous if it exhibits one or more of the following six characteristics in humans or animals [1.2.1, 1.3.1, 1.6.3]:
Carcinogenicity
This refers to the ability of a substance to cause cancer [1.2.6]. Drugs that are known or suspected human carcinogens fall into this category. The International Agency for Research on Cancer (IARC) often provides classifications that NIOSH uses in its evaluation [1.2.8].
Teratogenicity or Developmental Toxicity
Teratogenicity is the capacity to cause defects in a developing fetus [1.2.6, 1.3.7]. Developmental toxicity is a broader term that includes any adverse effects on the developing organism, which can occur from conception through puberty.
Reproductive Toxicity
This includes adverse effects on fertility and sexual function in both men and women [1.2.6]. Exposure to these drugs can lead to problems such as infertility or other reproductive harm [1.3.8].
Organ Toxicity at Low Doses
This criterion applies to drugs that can cause significant damage to one or more organs (e.g., liver, kidney, heart) even at very low doses [1.2.5, 1.6.5]. The toxicity is unrelated to the intended therapeutic effect and represents a significant risk to unintentionally exposed workers.
Genotoxicity
Genotoxicity is the ability of a chemical to damage the genetic information within a cell (DNA and chromosomes), causing mutations [1.2.6]. This damage can potentially lead to cancer.
Structure and Toxicity Profiles of New Drugs
New drugs that have a chemical structure and toxicity profile similar to an existing drug known to be hazardous are also classified as hazardous until more specific data becomes available [1.2.1, 1.6.3].
Common Categories of Hazardous Drugs
Hazardous drugs (HDs) are found across various therapeutic classes. The largest and most well-known group is antineoplastic agents, but many other types of medications are also on the NIOSH list [1.3.2, 1.3.5, 1.3.6].
- Antineoplastic Drugs: This includes all chemotherapy drugs used to treat cancer, such as cyclophosphamide, doxorubicin, and paclitaxel [1.3.1, 1.7.5].
- Antiviral Drugs: Certain antivirals, like ganciclovir and ribavirin, are considered hazardous [1.6.1, 1.7.2].
- Hormones: Many hormones and hormone antagonists, such as estradiol and tamoxifen, are listed due to their potential for reproductive toxicity [1.3.2, 1.7.5].
- Immunosuppressants: Drugs like tacrolimus and cyclosporine, which are used to prevent organ transplant rejection, are also classified as hazardous [1.7.2, 1.7.6].
- Bioengineered Drugs: This category includes a growing number of newer, complex medications that meet one or more of the NIOSH criteria [1.3.2].
The Gold Standard for Safety: USP General Chapter <800>
To address the risks posed by hazardous drugs, the U.S. Pharmacopeia (USP) created General Chapter <800>, which provides standards for safe handling in healthcare settings [1.2.2]. These standards are designed to protect healthcare personnel, patients, and the environment [1.3.3]. The chapter outlines comprehensive requirements for every stage of a drug's journey through a facility, including engineering controls, personal protective equipment (PPE), and disposal.
Comparison: Hazardous vs. Non-Hazardous Drug Handling
| Feature | Hazardous Drug Handling (per USP <800>) | Standard Drug Handling |
|---|---|---|
| Storage | Must be stored separately, often in a negative-pressure room, to prevent cross-contamination [1.4.3]. Refrigerated HDs require a dedicated refrigerator [1.4.5]. | Stored with general inventory on standard pharmacy shelving. |
| Compounding | Must occur in specific engineering controls, such as a Class II Biological Safety Cabinet (a C-PEC) located within a negative-pressure room (a C-SEC) [1.4.3]. | Performed in a standard cleanroom or segregated compounding area. |
| Personal Protective Equipment (PPE) | Requires two pairs of chemotherapy-rated gloves, an impermeable gown, and often eye/face and respiratory protection [1.4.3]. | A single pair of gloves may be sufficient, with less stringent gowning requirements. |
| Disposal | All waste, including used PPE, is considered contaminated and must be disposed of in specially marked containers according to federal, state, and local regulations [1.4.1, 1.4.4]. | Disposed of as standard pharmaceutical waste unless otherwise specified. |
| Training | Personnel must receive specific training on the risks and safe handling procedures for HDs and demonstrate competency [1.4.2, 1.4.3]. | General training on medication handling and aseptic technique. |
Routes of Exposure
Occupational exposure to hazardous drugs can happen in several ways [1.3.2, 1.5.7]:
- Dermal Absorption: Direct contact with the skin is a primary route of exposure.
- Inhalation: Aerosolized powders or droplets can be inhaled during compounding or administration.
- Ingestion: Accidental hand-to-mouth contact can lead to ingestion.
- Injection: Accidental needlesticks or sharps injuries pose a direct risk.
Conclusion: Fostering a Culture of Safety
Defining a drug as hazardous is the first step in a crucial safety process. The classification, guided by the rigorous NIOSH criteria, triggers a cascade of safety protocols outlined by USP <800>. From specialized engineering controls and mandatory PPE to meticulous training and disposal procedures, every measure is designed to minimize occupational exposure. For the millions of healthcare workers who handle these potent medications, understanding these risks and adhering to safety standards is paramount to protecting their own health and well-being.
For an authoritative list of these medications, see the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings.
