Section 12.3: Hazardous Drug Handling

Section 12.3: Hazardous Drug Handling

Safety during the handling of hazardous drugs (HDs) is governed by USP Chapter <800> and actively enforced by the Texas State Board of Pharmacy (TSBP) to protect pharmacy workers, patients, and the environment. Exposure to HDs can cause reproductive toxicity, fetal malformations, and mutagenic or carcinogenic effects.

Defining Hazardous Drugs (The NIOSH List)

USP <800> defines a hazardous drug as any drug identified as such by the National Institute for Occupational Safety and Health (NIOSH). The NIOSH list divides hazardous drugs into three categories based on their safety profile:

1. Group 1: Antineoplastic Drugs: Chemotherapy agents (e.g., cisplatin, doxorubicin, methotrexate, cyclophosphamide) representing the highest risk to handlers as known human carcinogens.
2. Group 2: Non-Antineoplastic Hazardous Drugs: Meet NIOSH toxicity criteria but are not cancer drugs. Examples include anticonvulsants (phenytoin, carbamazepine), certain immunosuppressants (cyclosporine), and hormones (estradiol, testosterone).
3. Group 3: Drugs with Primarily Reproductive Risks: Pose a danger to individuals who are pregnant, trying to conceive, or breastfeeding. Examples include finasteride, ganciclovir, spironolactone, and progesterone.

Under TSBP rules, a pharmacy must maintain a list of all hazardous drugs handled on-site, which must be updated at least annually.

Assessment of Risk (AoR)

USP <800> allows pharmacies to perform an Assessment of Risk (AoR) to exempt certain finished dosage forms or non-antineoplastic drugs from strict negative-pressure containment requirements:

• When Allowed: An AoR can be developed for finished commercial dosage forms (such as counting oral tablets of phenytoin or spironolactone) or Group 2 and Group 3 drugs where no active pharmaceutical ingredient (API) manipulation occurs. The AoR must document the specific drug, source, risk, and alternative containment strategies (e.g., using dedicated counting tools, separate spatulas, and wearing single gloves).
• When Prohibited: An AoR is never permitted for any antineoplastic active pharmaceutical ingredient (API) that requires manipulation (e.g., weighing raw methotrexate powder or reconstituting a sterile chemotherapy vial). Any manipulation of a Group 1 antineoplastic chemical must follow full containment controls.
• Review: All AoR documents must be in writing, signed by the PIC, and reviewed at least every 12 months.

Engineering Controls for Hazardous Drug Compounding

Compounding must be performed under negative-pressure conditions to prevent the escape of hazardous aerosols, dusts, and vapors. Engineering controls are divided into three levels:

1. Containment Primary Engineering Control (C-PEC)

The ventilated device designed to minimize worker exposure. For non-sterile HD compounding, a C-PEC can be a Class I Biological Safety Cabinet (BSC) or a containment ventilated powder hood. For sterile HD compounding, it must be a Class II or III BSC or a Compounding Aseptic Containment Isolator (CACI). All C-PECs used for sterile HD compounding must be externally vented to the outside air.

2. Containment Secondary Engineering Control (C-SEC)

The room in which the C-PEC is placed. The C-SEC must be a dedicated room physically separate from the general pharmacy. It must meet these parameters:

• Pressure: Maintain a negative pressure relative to surrounding non-hazardous areas (between -0.01 and -0.03 inches of water column).
• Venting: Must be externally vented through a dedicated exhaust fan to the outside atmosphere.
• Air Changes: For sterile HD compounding, the C-SEC must have at least 30 air changes per hour (ACPH). For non-sterile HD compounding, it must have at least 12 ACPH.

3. Containment Segregated Compounding Area (C-SCA)

An unclassified room that maintains negative pressure (-0.01 to -0.03 inches of water column) and has at least 12 ACPH. The C-PEC must be externally vented, and the maximum BUD for preparations compounded in a C-SCA is limited to 12 hours room temp or 24 hours refrigerated.

Personal Protective Equipment (PPE)

When compounding hazardous drugs, the following PPE is required:

• Double Chemotherapy Gloves: Personnel must wear two pairs of chemotherapy-rated gloves that meet ASTM D6978 standards. The outer glove must be sterile for sterile compounding. Gloves must be changed at least every 30 minutes during compounding, or immediately if torn or contaminated.
• Chemotherapy Gowns: A disposable gown shown to resist permeability by hazardous drugs must be worn. Gowns must be changed every 2 to 3 hours, or immediately upon contamination.
• Double Shoe Covers: Two pairs of shoe covers must be worn. The outer pair must be removed and discarded inside the C-SEC buffer room before stepping across the cleanroom threshold (often marked by a line of demarcation) into the ante-room. This prevents the tracking of hazardous drug residue outside the containment area.
• Respiratory Protection: An N95 respirator is acceptable for general particulate protection. However, when cleaning a hazardous spill or handling raw powders, a full-face piece chemical respirator or a Powered Air-Purifying Respirator (PAPR) must be worn.

Hazardous Spill Management and Disposal

Pharmacies handling hazardous drugs must maintain a hazardous spill kit in all areas where HDs are received, stored, or compounded. Only trained personnel wearing full PPE (including respirator masks) may clean a spill.

• Trace Waste (Yellow Containers): Items that have come into contact with hazardous drugs but do not contain bulk product (e.g., empty vials, used gowns, gloves) must be discarded in yellow trace waste containers.
• Bulk Waste (Black Containers): Vials or bags that contain residual or un-dispensed hazardous drug product must be treated as hazardous waste and disposed of in black bulk waste containers.