13.2 Hazardous Drug Handling (USP <800>)

13.2 Hazardous Drug Handling (USP <800>)

Healthcare workers who handle hazardous medications face documented occupational exposure risks, including skin rashes, reproductive toxicity, teratogenicity, genetic mutations, and secondary malignancies. USP General Chapter <800> (Hazardous Drugs — Handling in Healthcare Settings) establishes comprehensive, mandatory environmental, engineering, and personal safety standards designed to protect healthcare personnel, patients, and the environment. In Oklahoma, compliance with USP <800> is enforced across all pharmacy settings handling hazardous drugs (HDs) through the Oklahoma State Board of Pharmacy (OSBP) and federal Occupational Safety and Health Administration (OSHA) mandates.

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Scope & NIOSH Hazardous Drug Categorization

USP <800> applies to all healthcare personnel (pharmacists, pharmacy technicians, nurses, physicians, shipping/receiving personnel, and housekeeping staff) and all healthcare facilities where HDs are unpacked, stored, compounded, dispensed, transported, or administered.

NIOSH Criteria for Hazardous Drugs

A drug is classified as hazardous by the National Institute for Occupational Safety and Health (NIOSH) if it meets one or more of the following six toxicity criteria in humans or animals:

1. Carcinogenicity: Ability to induce cancer or increase its incidence;
2. Teratogenicity or Developmental Toxicity: Ability to cause birth defects or fetal harm;
3. Reproductive Toxicity: Ability to impair fertility or cause reproductive impairment;
4. Organ Toxicity at Low Doses: Ability to cause serious organ damage at therapeutic or sub-therapeutic dose thresholds;
5. Genotoxicity: Ability to induce DNA damage or chromosomal aberrations;
6. Structure and Toxicity Mimicry: New drugs with chemical structure and toxicity profiles resembling existing hazardous drugs.

NIOSH List of Hazardous Drugs: Three Operational Groups

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|                         NIOSH HAZARDOUS DRUG CLASSIFICATION                             |
+-----------------------------------------------------------------------------------------+
| GROUP 1: Antineoplastic Drugs                                                           |
| - Cytotoxic chemotherapy agents (e.g., cisplatin, cyclophosphamide, doxorubicin,        |
|   methotrexate, fluorouracil, paclitaxel, vincristine)                                  |
+-----------------------------------------------------------------------------------------+
| GROUP 2: Non-Antineoplastic Hazardous Drugs                                             |
| - Agents meeting toxicity criteria but not used in cancer therapy (e.g., cyclosporine,  |
|   azathioprine, carbamazepine, spironolactone, mycophenolate, tacrolimus)               |
+-----------------------------------------------------------------------------------------+
| GROUP 3: Hazardous Drugs with Primary Reproductive Risks                                |
| - Agents posing reproductive toxicity primarily to individuals who are pregnant,       |
|   breastfeeding, or actively attempting to conceive (e.g., finasteride, dutasteride,    |
|   letrozole, misoprostol, warfarin, clonazepam, oxytocin)                               |
+-----------------------------------------------------------------------------------------+

Assessment of Risk (AoR) Protocol

Entities must maintain a documented list of all HDs handled on site and review it at least annually (every 12 months). For certain formulations, an Assessment of Risk (AoR) may be performed:

• Eligible Formulations: Intact, solid dosage forms of Group 2 or Group 3 drugs, and antineoplastic agents that do not require manipulation (e.g., counting intact tablets or capsules of finasteride or tamoxifen for outpatient dispensing).
• Alternative Containment Strategies: If an AoR demonstrates minimal aerosolization risk, the entity may establish alternative containment strategies (e.g., dedicated counting trays, nitrile gloves, avoidance of automated counting robots).
• Ineligible Formulations: Active Pharmaceutical Ingredients (APIs) of ANY hazardous drug and any antineoplastic agent that must be manipulated (e.g., crushing tablets, opening capsules, pouring bulk powders, compounding sterile IV admixtures) CANNOT use an AoR and must strictly comply with all USP <800> engineering and containment controls.

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Containment Engineering Controls (C-PECs and C-SECs)

Engineering controls are organized into primary, secondary, and supplemental levels to contain airborne hazardous residues and volatile chemical vapors:

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|                   CONTAINMENT ENGINEERING CONTROL CLASSIFICATION                        |
+-----------------------------------------------------------------------------------------+
| 1. Containment Primary Engineering Control (C-PEC): Direct ventilated device (Hood)     |
| 2. Containment Secondary Engineering Control (C-SEC): The physical room housing C-PEC   |
| 3. Supplementary Controls (CSTDs): Closed-System Drug-Transfer Devices                  |
+-----------------------------------------------------------------------------------------+

Containment Primary Engineering Controls (C-PECs)

Strict Prohibition: Laminar Airflow Workstations (LAFWs) and Compounding Aseptic Isolators (CAIs) blow positive-pressure HEPA air directly toward the operator and MUST NEVER be used for hazardous drug handling under any circumstances.

Containment Secondary Engineering Controls (C-SECs)

The C-SEC is the physical room housing the C-PEC. It must adhere to rigorous structural and mechanical engineering criteria:

1. Physical Separation: The C-SEC must be a dedicated, physically enclosed room separated from non-hazardous preparation areas by solid walls and sealed doors.
2. External Exhaust: All room air and C-PEC exhaust must be vented directly to the outside atmosphere.
3. Negative Pressure Differential: The C-SEC must maintain continuous negative pressure relative to adjacent hallways and anterooms between -0.010 and -0.030 inches of water column (-2.5 to -7.5 Pascals) to draw air inward and prevent HD particle escape.
4. Air Changes Per Hour (ACPH):
   • Sterile HD Cleanroom (ISO Class 7 Buffer): Minimum 30 ACPH;
   • Non-Sterile HD Compounding Room: Minimum 12 ACPH;
   • Containment Segregated Compounding Area (C-SCA): Minimum 12 ACPH (used only for Category 1 HD CSPs with max 12h room temp / 24h cold BUD).
5. Anteroom for Sterile HDs: The anteroom leading into a negative-pressure sterile HD buffer room must be ISO Class 7 (unlike non-hazardous anterooms which can be ISO Class 8) and must maintain positive pressure (≥ +0.020 in. w.c.) relative to general external corridors, creating a clean air lock.

Supplemental Controls: Closed-System Drug-Transfer Devices (CSTDs)

Closed-System Drug-Transfer Devices (CSTDs) are supplemental engineering controls that mechanically prohibit the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system:

• During Compounding: CSTDs are recommended during reconstitution and compounding inside a C-PEC.
• During Administration: CSTDs are MANDATORY for the administration of antineoplastic hazardous drugs by healthcare personnel (nursing staff) whenever the dosage form allows (e.g., IV piggyback infusions, syringe injections).

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Personal Protective Equipment (PPE) Standards

PPE provides a crucial physical barrier against hazardous chemical dermal absorption, mucosal splashes, and inhalation.

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|                             USP <800> PPE REQUIREMENTS                                  |
+-----------------------------------------------------------------------------------------+
| Gloves     | TWO pairs of chemotherapy-tested gloves (ASTM D6978 compliant).            |
|            | Inner glove under gown cuff; outer glove OVER gown cuff.                   |
|            | Change every 30 MINUTES or immediately if torn/contaminated.               |
+------------+----------------------------------------------------------------------------+
| Gowns      | Disposable, lint-free, low-permeability (polyethylene-coated/laminate).    |
|            | Must close in the BACK with long sleeves and tight elastic/knit cuffs.     |
|            | Change every 2 TO 3 HOURS or immediately following a spill/splash.         |
+------------+----------------------------------------------------------------------------+
| Respiratory| N95 respirator protects against airborne particles ONLY (not vapors).      |
|            | PAPR (Powered Air-Purifying Respirator) or elastomeric half-mask with gas  |
|            | / vapor chemical cartridge required for spills and C-PEC deep cleaning.    |
+------------+----------------------------------------------------------------------------+
| Eye / Face | Full face shield COMBINED with safety goggles for splash hazards.          |
|            | Safety glasses with side shields are INADEQUATE for splash protection.     |
+------------+----------------------------------------------------------------------------+
| Shoe Covers| TWO pairs of shoe covers required for sterile HD cleanrooms.               |
|            | Outer shoe covers donned before entering C-SEC and removed when exiting.   |
+-----------------------------------------------------------------------------------------+

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Surface Decontamination, Cleaning, and Disinfection Protocol

Surfaces inside C-PECs and C-SECs must be cleaned following a strict, mandatory four-step sequential cycle using appropriate chemical agents to eliminate chemical residues and biological contaminants:

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|                    4-STEP HAZARDOUS SURFACE DECONTAMINATION CYCLE                       |
+-----------------------------------------------------------------------------------------+
| 1. DEACTIVATION    --> Inactivates HD residue using EPA-registered oxidizers            |
|                        (e.g., 2% Sodium Hypochlorite / Bleach, Hydrogen Peroxide)       |
|                             |
| 2. DECONTAMINATION --> Neutralizes, dissolves, or physically removes HD residue         |
|                        (e.g., Sodium Thiosulfate neutralizer, Sterile Water wipe)       |
|                             |
| 3. CLEANING        --> Removes organic and inorganic soils and surfactants              |
|                        (e.g., Germicidal detergent, Quaternary Ammonium surfactant)     |
|                             |
| 4. DISINFECTION    --> Destroys viable microorganisms (Sterile areas only)              |
|                        (e.g., Sterile 70% Isopropyl Alcohol - IPA)                      |
+-----------------------------------------------------------------------------------------+

Stainless Steel Corrosion Warning: Bleach (sodium hypochlorite) causes severe pitting and corrosion on stainless steel hood surfaces. Therefore, sodium hypochlorite deactivation must immediately be followed by a neutralizing decontaminant such as sodium thiosulfate or sterile water.

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Spill Management, Disposal, and Medical Surveillance

Spill Kit Availability & Immediate Action

• Spill Kit Placement: Commercial HD spill kits must be immediately accessible wherever hazardous drugs are handled, including receiving docks, storage rooms, compounding suites, and nursing units.
• Kit Contents: Must include chemotherapy-rated PPE (gloves, gown, goggles, N95/respirator, shoe covers), chemical-absorbent pads, neutralizer/decontaminant, disposable plastic scoop and scraper (never pick up broken glass by hand), hazardous waste bags, and warning perimeter caution signs.

Hazardous Waste Segregation & Labeling

• Yellow Chemotherapy Bins (Trace Chemo Waste): Used for empty vials, empty IV bags, syringes, needles, tubing, and used PPE containing trace HD residue (< 3% by weight). Incinerated at regulated medical waste temperatures.
• Black Hazardous Waste Bins (Bulk Chemo Waste / RCRA Hazardous): Used for partially full HD vials, expired medications, spill cleanup debris, and containers with > 3% remaining volume. Regulated under the Resource Conservation and Recovery Act (RCRA).

Medical Surveillance Program (OSHA / USP <800>)

Healthcare employers must establish an ongoing medical surveillance program for all personnel with routine occupational exposure to HDs:

• Baseline Health Screening: Comprehensive medical and reproductive history, physical examination, and baseline laboratory testing (complete blood count - CBC with differential, renal and hepatic panels);
• Ongoing Monitoring: Periodic health evaluations and immediate post-exposure medical evaluations following accidental spills or needle-sticks;
• Record Retention: Under OSHA standard 29 CFR § 1910.1020, employee occupational exposure and medical surveillance records must be maintained by the employer for the duration of employment plus 30 years.