Hazardous Drugs

Foundations of Hazardous Drug Compounding Safety

Hazardous drugs (HDs) are medications that pose significant health risks to healthcare workers, patients, and the environment through occupational exposure. Compounding of hazardous drugs—whether sterile (e.g., chemotherapy) or nonsterile (e.g., some hormones)—requires strict adherence to safety standards to prevent contamination, toxic effects, and regulatory violations. This topic is a high-yield area on the Pharmacy Technician Certification Exam (PTCE) and is essential for safe practice in hospital and specialty pharmacies.^[1]

Essential Terminology for Hazardous Drug Handling

Hazardous Drug (HD)

Any drug identified by the National Institute for Occupational Safety and Health (NIOSH) as meeting one or more of the following criteria: carcinogenicity, teratogenicity, reproductive toxicity, genotoxicity, or organ toxicity at low doses.^[2] NIOSH publishes an updated list categorized by risk level.

USP <800>

United States Pharmacopeia general chapter that sets the minimum practice standard for the safe handling of hazardous drugs in healthcare settings. It applies to all personnel involved in receiving, storing, compounding, dispensing, administering, and disposing of HDs.^[1]

Containment Primary Engineering Control (C-PEC)

A device used to provide worker protection during compounding, such as a biological safety cabinet (BSC) (Class II Type A2 or B2) or a containment isolator (e.g., closed-system transfer device). The C-PEC exhausts air through HEPA filters.^[3]

Containment Secondary Engineering Control (C-SEC)

The room or area that houses the C-PEC. For sterile compounding, the C-SEC includes a buffer room (ISO Class 7 air) and an anteroom (ISO Class 7 or 8). For nonsterile compounding, a dedicated area with negative or neutral pressure relative to adjacent spaces is required.^[1]

Closed System Transfer Device (CSTD)

A drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous vapor or aerosol out of the system. CSTDs are recommended for all HD administration and compounding.^[4]

Operational Standards and Compliance Workflows

USP <800> Compliance Framework

Risk Assessment: Identify all HDs handled (NIOSH list + facility-specific). Determine containment level using the NIOSH Hazardous Drug Exposure Assessment form or similar tool.^[2]
Standard Operating Procedures (SOPs): Written protocols for receiving, storing, compounding, dispensing, administering, and waste disposal of HDs.
Engineering Controls:
- Sterile HD compounding: C-PEC (BSC or isolator) inside a buffer room with negative pressure relative to the anteroom.
- Nonsterile HD compounding: Containment ventilated enclosure (CVE) or dedicated area with HEPA filtration and negative pressure.
Work Practices:
- Use CSTDs for all mixing and administration when drug form allows.
- Perform compounding only in C-PEC; keep work surface clean and clutter-free.
- Wear appropriate personal protective equipment (PPE): double gloves (tested for HD permeability), disposable gown (no cuffs), eye/face shield if splash risk.
Training: All staff must complete initial and annual hands-on competency assessment on HD handling procedures.^[1]
Medical Surveillance: Employer must offer baseline and periodic health assessments, including blood work for possible exposure effects.
Waste Disposal: HD waste (traces of drug, contaminated PPE, sharps) must be segregated and placed in labeled, leak-proof, puncture-resistant containers, and disposed per federal/state regulations (EPA RCRA).

Receiving and Storage

HDs should be received in a separate area away from non-hazardous stock. Use designated carts or bins.
Store HDs in a negative-pressure or externally ventilated area, separate from other inventory.
Outer shipping containers may be contaminated; staff must wear chemotherapy gloves when opening.^[3]

Compounding Workflow (Sterile HD)

Assemble all components (vials, diluents, CSTD, syringes) inside the C-PEC.
Perform hand hygiene, then don sterile PPE (gloves, gown, mask if required).
Using aseptic technique and closed-system devices, transfer drug from vial to final container (bag, syringe).
Label product with appropriate “HAZARDOUS DRUG” auxiliary label and handling precautions.
Decontaminate work surface and all equipment inside C-PEC after each batch or every shift.

Recognizing Contamination and Exposure Indicators

Surface contamination: Identified through wipe sampling (e.g., cyclophosphamide detection on counters, floors, chairs).
Acute employee symptoms: Skin rash, eye irritation, nausea, dizziness—may indicate improper PPE or spills.
Chronic exposure risks: Long-term links to leukemia, other cancers, reproductive harm (miscarriage, birth defects).^[5]

Monitoring and Surveillance Strategies for HD Safety

Environmental Monitoring

Periodic surface wipe sampling for HD residues (e.g., cyclophosphamide, ifosfamide, methotrexate). Action levels set by facility.
Air sampling in C-PEC rooms to verify HEPA integrity and pressurization.

Medical Surveillance

Pre-placement health questionnaire, physical exam, baseline blood work (CBC, liver enzymes, urinalysis).
Periodic (e.g., annual) reassessment; reporting of any exposure incidents.

Spill Response and Decontamination Procedures

Spill Cleanup Procedure

Evacuate area; restrict access.
Don spill kit PPE: double chemotherapy gloves, impermeable gown, face shield, respirator (N95 or higher) if large spill or powder.
Cover spill with absorbent pads (e.g., spill-control pillows or absorbent sheets) to contain liquid.
For powder spills, use damp pads to avoid aerosolization; never sweep or dry wipe.
Clean area first with detergent/deactivation solution (e.g., 1% sodium hypochlorite or commercial HD cleaner), then with sterile water or alcohol for decontamination.
Place all waste in HD waste container; label as “HAZARDOUS DRUG WASTE”.
Notify supervisor; document incident per facility policy.^[4]

Risk Mitigation and Protective Measures

PPE failures: Latex or nitrile gloves may not protect against all HDs; use gloves that have been tested for permeability to the specific drug (listed by manufacturer). Double-gloving is mandatory.
Cross-contamination: Never store HDs with non-hazardous products in the same shelving unit. Use separate carts for transport.
Sharps hazard: Needles, syringes, and broken vials must be placed in puncture-resistant sharps containers designated for HD waste.
Vapor exposure: Some HDs (e.g., carmustine, cyclophosphamide) volatilize at room temperature; use CSTDs and closed-system compounding.
Pregnancy and breastfeeding: Staff who are pregnant, trying to conceive, or breastfeeding should be offered reassignment away from HD handling duties (per OSHA recommendation).^[5]

Essential Knowledge for Certification Success

Know the three NIOSH categories:
- Group 1: Antineoplastics (e.g., cisplatin, doxorubicin) – highest risk.
- Group 2: Non-antineoplastics that meet one or more hazard criteria (e.g., hormones, immunosuppressants).
- Group 3: Drugs with reproductive risk only (e.g., clonazepam, misoprostol).^[2]
USP <800> vs <797>: <797> covers sterile compounding (non-hazardous and hazardous); <800> applies only to hazardous drugs. Both must be followed for sterile HD compounding.
PPE requirements: Exam likes to test specifics: double gloves, gown (closed-front, cuffs, back closure), eye/face protection when needed, N95 or higher respirator for powder or aerosol-prone drugs.
C-PEC types: BSC Class II B2 (100% exhaust) is required for sterile HD compounding with volatile drugs; A2 may be used for non-volatile if placed in a negative-pressure room.
Antineoplastic spill kit: Must be available wherever HDs are handled. Contains gloves, gown, shoe covers, goggles, respirator, absorbent pads, scoop, and waste bags.
Memory aid for spill steps: “D-E-C-O-N” (Don PPE, Evacuate, Contain, Clean, Dispose and Document).