11.4 Hazardous Drug Handling (USP <800>): Engineering Controls & Personal Protective Equipment

11.4 Hazardous Drug Handling (USP <800>): Engineering Controls & PPE

MPJE Core Concept: USP General Chapter <800> defines worker and environmental protection standards across the entire life cycle of Hazardous Drugs (HDs). Unlike USP <795> and <797> which focus on patient safety, USP <800> focuses on occupational exposure prevention. Key MPJE test points include C-SEC negative pressure ranges, air change per hour (ACPH) rules, ASTM D6978 chemotherapy gloves, and the 4-step decontamination workflow.

Scope & NIOSH Hazardous Drug Categorization

USP <800> applies to all healthcare personnel who receive, store, compound, dispense, administer, or dispose of hazardous drugs. The chapter adopts the National Institute for Occupational Safety and Health (NIOSH) List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, which categorizes HDs into three groups:

1. Group 1: Antineoplastic drugs (e.g., cisplatin, cyclophosphamide, fluorouracil, vincristine).
2. Group 2: Non-antineoplastic hazardous drugs meeting one or more NIOSH toxicity criteria (e.g., spironolactone, carbamazepine, divalproex).
3. Group 3: Drugs that primarily pose reproductive risk to male or female personnel (e.g., misoprostol, dutasteride, finasteride).

Entity Assessment of Risk (AoR)

An entity (pharmacy/hospital) may perform an Assessment of Risk (AoR) for Group 2, Group 3, or final dosage forms of Group 1 HDs to define alternative handling strategies, provided the HDs do not require manipulation other than counting or packaging. If no AoR is performed, all HDs must be handled strictly according to full USP <800> containment rules.

Engineering Controls Architecture (C-PECs, C-SECs, C-SCAs)

USP <800> mandates containment engineering controls specifically designated with a "C-" prefix to isolate HD contaminants:

1. Containment Primary Engineering Control (C-PEC)

A ventilated device designed to minimize worker exposure during HD handling:

• For Sterile HD Compounding: Class II Biological Safety Cabinet (BSC Type A2, B1, or B2) or Compounding Aseptic Containment Isolator (CACI). Must be externally vented.
• For Non-Sterile HD Compounding: Class I BSC, Class II BSC, or Containment Ventilated Enclosure (CVE / powder hood). Must be externally vented (or, as a strict exception for non-sterile compounding only, redundant HEPA filters in series may be permitted where external venting is unavailable).

2. Containment Secondary Engineering Control (C-SEC)

The physical room in which the C-PEC is placed. The C-SEC must meet three strict engineering criteria:

1. Physical Separation: Must be a dedicated, physically enclosed room separated from non-HD compounding areas.
2. External Venting: Must be externally vented to the outside atmosphere.
3. Negative Pressure Differential: Must maintain continuous negative pressure between 0.01 and 0.03 inches of water column (-2.5 to -7.5 Pascals) relative to adjacent areas.

Air Changes Per Hour (ACPH) Requirements

• Non-Sterile HD Compounding C-SEC: Minimum 12 ACPH.
• Sterile HD Compounding C-SEC (ISO Class 7): Minimum 30 ACPH.
• Containment Segregated Compounding Area (C-SCA): Minimum 12 ACPH under negative pressure (0.01 to 0.03 inches w.c.) and externally vented. Used only for low-volume or Category 1 sterile HD compounding (BUD capped at 12 hours room temp / 24 hours refrigerated).

Personal Protective Equipment (PPE) for HD Handling

PPE provides a physical barrier against hazardous drug splashes, aerosols, and surface residue. All PPE used for HD compounding must be disposable and properly discarded as hazardous drug waste.

1. Chemotherapy Gloves

• Testing Standard: Gloves must be tested and rated under ASTM D6978 (a standard specifically designed to evaluate permeation by chemotherapy drugs). Standard medical exam gloves tested under ASTM D3578 are unacceptable.
• Double Glove Requirement: Personnel must wear TWO pairs of chemotherapy gloves for all HD compounding, administration, spill handling, and disposal.
• Sterility: When compounding sterile HDs, the outer pair of chemotherapy gloves must be sterile.
• Donning Rules: The inner glove must be worn under the gown cuff; the outer glove must be pulled over the gown cuff.
• Replacement Frequency: Gloves must be changed at least every 30 minutes, or immediately if damaged, torn, or contaminated.

2. Isolation Gowns

• Gowns must be shown to resist permeation by HDs (laminated, polyethylene-coated or impermeable material).
• Must be back-closing, seamless, lint-free, with long sleeves and tight-fitting elastic or knit cuffs.
• Gowns must be changed every 2 to 3 hours or immediately after a spill or splash.

3. Shoe & Hair Covers

• Double Shoe Covers: Two pairs of shoe covers are required when compounding sterile HDs. Outer shoe covers must be donned before entering the negative-pressure C-SEC and removed when exiting the C-SEC to prevent spreading HD residue to unclassified corridors.

4. Eye, Face & Respiratory Protection

• Eye & Face Protection: Full face shield plus goggles must be worn when there is a risk of HD splashes, sprays, or aerosolization (e.g., cleaning C-PEC drain pans, spill cleanup). Standard safety glasses with side shields do NOT provide adequate splash protection.
• Respiratory Protection: An N95 respirator protects against solid particulate powders but does not protect against HD vapors. A Powered Air-Purifying Respirator (PAPR) or elastomeric half-mask with P100 filter is mandatory during HD spill cleanup, handling bulk API powders, or servicing C-PEC components.

Mandatory 4-Step Decontamination & Cleaning Workflow

Cleaning HD handling areas requires a strict, sequential 4-step process to neutralize, remove, and disinfect surfaces:

1. Deactivation: Renders the hazardous drug compound inactive or non-toxic using EPA-registered oxidizers (e.g., sodium hypochlorite / bleach, hydrogen peroxide, or peracetic acid).
2. Decontamination: Removes inactivated HD residue and chemical deposits from surfaces using sterile water, 70% alcohol, or specialized HD decontamination wipes.
3. Cleaning: Removes organic and inorganic soil from surfaces using a germicidal detergent.
4. Disinfection: Destroys vegetative microorganisms (mandatory in sterile compounding areas) using 70% Sterile Isopropyl Alcohol (IPA).

Summary of Hazardous Drug Engineering Standards