3.3 Hazardous Non-Sterile Handling & Quality Assurance

Hazardous Non-Sterile Handling & Quality Assurance

Core Principle: Handling hazardous pharmaceuticals during non-sterile compounding presents significant toxicological risks to pharmacy personnel and the environment. Under the NAPRA Model Standards and occupational health guidelines, pharmacy technicians must employ specialized engineering controls, chemotherapy-tested personal protective equipment (PPE), rigorous chemical deactivation protocols, and comprehensive quality assurance testing before releasing compounded preparations.

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1. Identifying Hazardous Drugs (HDs) & Toxicological Profiles

Pharmacy personnel must recognize hazardous drugs before unpacking, handling, or compounding them. In Canada, hazardous drug identification relies on the National Institute for Occupational Safety and Health (NIOSH) list and the Workplace Hazardous Materials Information System (WHMIS 2015).

NIOSH Hazardous Drug Lists: 2016 Groups vs. 2024 Tables

NAPRA's compounding standards (2016 and 2018) refer to the 2016 NIOSH List, which sorted hazardous drugs into three groups:

1. Group 1: Antineoplastic drugs (e.g., methotrexate, cyclophosphamide, fluorouracil, tamoxifen, hydroxyurea).
2. Group 2: Non-antineoplastic hazardous drugs (e.g., azathioprine, cyclosporine, carbamazepine, phenytoin).
3. Group 3: Drugs that are primarily reproductive or developmental hazards (e.g., finasteride, dutasteride, misoprostol, ganciclovir, testosterone, estrogens).

The NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 (published December 2024) reorganized the list into two tables:

• Table 1: Drugs that have manufacturer's special handling information (MSHI) and/or meet the NIOSH hazardous-drug definition and are classed as known or probable human carcinogens. Not all Table 1 drugs are antineoplastics.
• Table 2: Other drugs that meet the NIOSH definition, including those that are only developmental or reproductive hazards.

For the exam, recognize both formats. The practical question is the same either way: is this drug hazardous, and what containment and PPE does the pharmacy's risk assessment require?

Toxicological Hazard Criteria

A medication is classified as a hazardous drug if animal or human studies demonstrate any of the following characteristics:

• Carcinogenicity: Ability to initiate or promote malignant tumor development.
• Teratogenicity / Developmental Toxicity: Ability to cause fetal malformations, structural defects, or fetal demise.
• Reproductive Toxicity: Impairment of fertility, abnormal menstrual cycles, or adverse reproductive outcomes.
• Organ Toxicity at Low Doses: Ability to induce serious target organ damage (e.g., nephrotoxicity, hepatotoxicity, pulmonary fibrosis) at standard therapeutic doses.
• Genotoxicity / Mutagenicity: Ability to damage DNA structure or induce chromosomal mutations.
• Structure-Activity Mimicry: New chemical entities possessing molecular structures closely resembling established hazardous drugs.

WHMIS 2015 & Safety Data Sheets (SDS)

Under Canadian workplace regulations, pharmacies must maintain an indexed library of Safety Data Sheets (SDS) for every chemical and hazardous bulk powder handled. The SDS contains 16 standardized sections detailing toxicological endpoints, exposure limits, handling safeguards, and spill disposal instructions. Technicians must look for the Health Hazard pictogram (a silhouette of a human head and chest with an exploding white internal star), which designates chronic health risks including carcinogenicity, germ cell mutagenicity, and reproductive toxicity.

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2. Engineering Controls for Hazardous Compounding (NAPRA Level C)

Handling hazardous powders in non-sterile compounding requires containment engineering controls that prevent airborne dust from escaping into general pharmacy areas.

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3. Personal Protective Equipment (PPE) for Hazardous Compounding

Personal protective equipment acts as the final barrier between hazardous chemical particulates and the compounding technician. All PPE must be donned prior to entering the C-SEC and entering the C-PEC work zone:

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1. Chemotherapy-Tested Gloves: Must meet ASTM D6978 standards for resistance to chemotherapy permeation. Powder-free nitrile or neoprene gloves are required (powder binds hazardous residues). Technicians must double-glove: the inner glove is placed beneath the gown sleeve cuff, and the outer glove is pulled completely over the gown cuff. Outer gloves must be replaced every 30 minutes, or immediately if torn, punctured, or contaminated.
2. Protective Gown: Disposable, lint-free gown constructed of non-permeable material (polyethylene-coated or polypropylene laminated). Must feature a closed front, long sleeves with snug knit or elastic cuffs, and fasten in the back. Gowns must be replaced every 2 to 3 hours, or immediately following a spill.
3. Respiratory Protection: A fit-tested, NIOSH-certified particulate filtering respirator (N95, N99, N100, or P100). Critical Distinction: Standard surgical masks do not form a tight facial seal and do not have rated particulate filter media; surgical masks provide zero respiratory protection against airborne hazardous drug dust.
4. Eye & Face Protection: Chemical splash goggles must be worn when manipulating hazardous liquids or when an aerosol risk exists. Standard safety glasses with side shields are inadequate against splashing liquids. A full-face shield is required if there is a risk of spraying.
5. Head & Shoe Covers: Technicians must wear disposable hair covers, beard covers (if applicable), and double shoe covers. The outer pair of shoe covers must be removed and discarded into a hazardous waste bin inside the C-SEC immediately before stepping out into the ante area.

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4. Decontamination, Deactivation, Cleaning & Disinfection

Cleaning a hazardous non-sterile containment hood is fundamentally different from cleaning standard equipment. Disinfecting with alcohol alone does not remove or neutralize hazardous chemical residues; it simply spreads hazardous molecules across the stainless steel surfaces.

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5. Hazardous Drug Spill Management

Every pharmacy compounding Level C preparations must maintain a dedicated, clearly marked Hazardous Drug Spill Kit stationed both inside and immediately outside the negative-pressure compounding suite.

Spill Kit Contents

• Full hazardous PPE: impermeable chemotherapy gown, two pairs of ASTM D6978 gloves, chemical splash goggles, NIOSH N95/P100 respirator, double shoe covers.
• Chemical-absorbent spill pads and neutralizing spill absorbent powder.
• Disposable plastic scoop and scraper (never use a broom, brush, or metal pan).
• Puncture-resistant sharps/broken glass container.
• Thick, leak-resistant hazardous (cytotoxic) waste bags labelled for your province's cytotoxic waste stream.
• Deactivation/decontamination wipes (bleach/oxidizer and neutralizer).
• Warning perimeter tape and "Caution: Hazardous Chemical Spill" signage.

Step-by-Step Spill Response Sequence

1. Alert & Isolate: Immediately notify all personnel in the pharmacy. Clear the area and post warning signs. Isolate the room to prevent foot traffic from spreading contamination.
2. Assess Magnitude: Determine spill size (small spill: <5 mL or 5 g; large spill: >5 mL or 5 g requiring specialized safety protocols).
3. Don Spill PPE: Put on complete spill PPE from the kit before approaching the spill.
4. Contain the Liquid or Powder:
   • Liquid Spills: Gently place chemical-absorbent pads over the liquid, working from the perimeter inward to prevent spreading the fluid outward.
   • Powder Spills: Gently place a damp, absorbent pad over the powder to prevent hazardous dust from aerosolizing into the air currents.
5. Remove Broken Glass & Debris: Use the disposable plastic scoop and scraper to collect broken glass or saturated pads. Never use bare or gloved hands to pick up broken glass. Deposit all sharp debris into the puncture-resistant container.
6. Perform 4-Stage Surface Cleaning: Deactivate, decontaminate, clean, and disinfect the entire spill area and surrounding perimeter.
7. Waste Disposal: Place all used absorbent pads, disposable cleaning tools, and contaminated PPE into the cytotoxic waste bag. Seal it and place it in the designated cytotoxic waste container for incineration.
8. Wash & Document: Remove gloves and wash hands thoroughly with soap and water. Complete a formal entry in the pharmacy Incident & Spill Log, detailing drug name, estimated volume, cause, corrective actions, and personnel involved.

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6. Finished Product Quality Assurance & Release

Before any non-sterile compounded preparation is released for patient dispensing, a registered pharmacy technician must perform and document comprehensive quality assurance checks:

1. Weight Variation Testing: For divided solid dosage forms (e.g., powder capsules, troches, suppositories), weigh 10 individual units and calculate the average weight. Individual weights must fall within specified tolerance limits (typically within ±10% of the target theoretical weight, or ±5% for narrow-therapeutic-index APIs).
2. Physical Stability Inspection:
   • Color & Uniformity: Ensure uniform color throughout without mottling, streaks, or discoloration.
   • Clarity & Particulates: Liquid solutions must be inspected against black and white backgrounds to verify complete dissolution and absence of foreign particulate matter.
   • Suspension Resuspendability: Verify that oral suspensions resuspend completely and evenly with moderate manual shaking, without persistent caking or sedimentation at the container base.
   • Emulsion Integrity: Verify that emulsions show no evidence of creaming, phase separation, or "cracking" (irreversible oil-water separation).
   • Semisolid Texture: Creams, ointments, and gels must be evaluated for tactile smoothness, absence of grittiness, and absence of syneresis (liquid weeping).
3. pH Verification: For aqueous oral or topical liquids, measure pH using a calibrated electronic pH meter or narrow-range pH indicator strips. Verify that the measured pH matches the stability range specified in the Master Formulation Record.
4. Independent Technical Verification Sign-Off: The registered pharmacy technician verifies calculations, ingredients, commercial lots, scale measurements, auxiliary warning labels, and assigned BUD before presenting the preparation and Compounding Record to the verifying professional for final release.