4.2 USP <800> & NIOSH Hazardous Drug Handling

USP General Chapter <800>

USP <800> ("Hazardous Drugs—Handling in Healthcare Settings") is the national standard for handling hazardous drugs (HDs) across the entire medication-use process — receipt, storage, compounding, dispensing, administration, and disposal. It became compendially applicable on November 1, 2023, alongside the revised USP <795> and <797>; enforcement in practice comes through state boards of pharmacy, accreditation bodies, and OSHA's general duty clause. It applies to all healthcare personnel and all entities that handle HDs, including pharmacies. The National Institute for Occupational Safety and Health (NIOSH) publishes the list of drugs it considers hazardous; this list is the reference for identifying which drugs USP <800> covers. The current edition is the NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 (published December 2024), which replaced the 2016 list.

How the NIOSH List Is Organized

The 2016 list used three groups: antineoplastic drugs, non-antineoplastic hazardous drugs, and drugs posing reproductive risk. The 2024 list collapses that into two tables, and the sorting rule changed — it is now driven by carcinogenicity classification and by whether the package insert carries manufacturer's special handling information (MSHI):

Two changes matter for the exam. First, Table 1 is no longer synonymous with "antineoplastic" — under the 2024 list, not every Table 1 drug is a chemotherapy agent. Second, the separate reproductive-hazard group is gone; those drugs now sit in Table 2.

A drug appears on the NIOSH list if it meets one or more of NIOSH's criteria: carcinogenicity, genotoxicity, developmental or reproductive toxicity, organ toxicity at low doses, or structural/toxicity similarity to a drug that meets those criteria.

Engineering Controls

USP <800> requires containment through engineering controls:

• Biological Safety Cabinet (BSC) — a ventilated cabinet for compounding HDs that provides personnel and product protection.
• Compounding Aseptic Containment Isolator (CACI) — a closed isolator providing both aseptic (USP <797>) and containment control; preferred for sterile HD compounding.
• Closed System Drug-Transfer Device (CSTD) — a device that mechanically prohibits transfer of contaminants or drug/vapor outside the system; used during compounding and administration to contain HDs.

Sterile HD compounding must occur in a containment primary engineering control (C-PEC), such as a BSC or CACI, placed inside a containment secondary engineering control (C-SEC), a negative-pressure HD compounding room.

Personal Protective Equipment (PPE)

Required PPE for HD handling includes:

• Double chemo gloves — tested to ASTM standards for chemotherapy
• Chemo gowns — impervious, closed-front, long-sleeved, with cuffs
• Respiratory protection — when engineering controls are insufficient or during spills (e.g., N95 or a powered air-purifying respirator)
• Eye and face protection — when splash risk exists
• Shoe covers and hair covers — as needed in compounding areas

Containment: Primary and Secondary

Primary containment isolates the hazard at the source (the C-PEC or CSTD). Secondary containment limits spread beyond the source (the negative-pressure room, contained storage bins). HDs must be stored separately from non-HDs in a designated negative-pressure area to prevent contamination of other inventory — a key supply-chain control.

Assessment of Risk (AoR)

For HDs other than antineoplastics requiring manipulation (and other than any active pharmaceutical ingredient), USP <800> permits an Assessment of Risk (AoR): the entity may document an alternative containment strategy if the drug's dosage form or use does not pose a contamination risk (e.g., a solid oral tablet packaged in a unit-dose). The AoR must be documented in writing and reviewed periodically. Antineoplastic agents are not eligible for AoR alternative containment — they always require full containment.

Spill Response and Spill Kits

Pharmacies handling HDs must have HD spill kits and written spill procedures. A spill response requires: donning double chemo gloves, a chemo gown, and a respirator; containing the spill with absorbent material; cleaning with the appropriate agent; disposing of all contaminated material as hazardous waste; and documenting the incident. Personnel exposure must be reported through the facility's medical surveillance program.

Medical Surveillance

Entities handling HDs must maintain a medical surveillance program that monitors personnel for exposure. Baseline and periodic monitoring, exposure-incident documentation, and reproductive risk counseling are components.

Supply-Chain Handling: Receiving and Storage

From the supply-chain angle, HDs must be handled safely at receipt and storage. Receiving personnel must inspect HD packages for damage (a damaged chemo vial is a spill event), store HDs in a designated containment area separate from non-HD stock, and label storage areas clearly. Storage bins and refrigerators holding HDs must carry warning labels (e.g., a chemotherapy hazard sign) so that all staff — including float and receiving personnel — recognize the hazard. Refrigerated HDs must be stored in a dedicated refrigerator inside the negative-pressure HD area, separate from non-HD refrigerated stock. Wastage and returned HDs must be segregated and disposed of as hazardous waste; reverse distributors must accept HDs with proper documentation.

Worked Scenario: A Damaged Vial at Receiving

A technician unboxing a shipment spots a chemotherapy vial with a crack and a small liquid leak inside the secondary packaging. This is not a routine return — it is an HD spill event at receiving. The technician dons double chemo gloves and a chemo gown, uses the spill kit to contain and absorb the leak, places the vial and all contaminated packaging into a hazardous waste container, and documents the incident in the HD handling log and the spill log. The receiving record is annotated to flag the damaged unit, and the wholesaler is notified for credit or replacement. Because the leak was contained to the shipping carton, no other inventory is affected — but if other stock had been contaminated, those units would also be quarantined and assessed. Prompt containment, correct PPE, and complete documentation protect both staff and the program during an HRSA or USP <800> review.