5.5 Sterile Compounding & Hazardous Drug Handling

5.5 Sterile Compounding & Hazardous Drug Handling

Sterile Compounding Standards (16 CCR § 1751 & USP <797>)

Sterile compounding involves the preparation of medications that bypass the body's natural defense mechanisms, such as intravenous (IV) infusions, intramuscular injections, and ophthalmic drops. Because microbial contamination of these products can lead to severe infection, sepsis, and death, the regulations are incredibly stringent. In California, sterile compounding is governed by 16 CCR § 1751 and USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations.

Crucially, any pharmacy performing sterile compounding in California must possess a specialized Sterile Compounding License issued by the Board of Pharmacy, in addition to their standard pharmacy license. The Board conducts rigorous annual inspections of these facilities.

The Cleanroom Environment

Sterile preparations must be compounded in a controlled environment to minimize the introduction of airborne particles and microorganisms. This environment is defined by ISO (International Organization for Standardization) classifications, which measure the number of particles per cubic meter of air. A lower ISO number indicates cleaner air.

1. Primary Engineering Control (PEC): This is the actual hood or cabinet where compounding takes place. It must maintain ISO Class 5 air quality. Examples include a Laminar Airflow Workbench (LAFW) or a Biological Safety Cabinet (BSC).
2. Buffer Room (Secondary Engineering Control - SEC): This is the room that houses the PEC. It must maintain ISO Class 7 air quality. The air in this room is heavily filtered (HEPA) and usually kept under positive pressure to prevent dirty air from entering.
3. Ante Room: This is the transition space between the unclassified general pharmacy area and the Buffer Room. It is used for hand hygiene, donning Personal Protective Equipment (PPE) (garbing), and staging components. It must maintain ISO Class 8 air quality (or ISO Class 7 if it opens into a negative pressure hazardous buffer room).

Maintaining these distinct zones requires precise engineering. HEPA filters are essential components that remove 99.97% of airborne particles 0.3 micrometers or larger. Airflow in the PEC is designed to be unidirectional, sweeping particles away from the critical compounding site. Any disruption in this airflow, such as rapid hand movements or overcrowding the hood with supplies, significantly increases the risk of contamination.

Personnel Competency and Testing

Humans are the largest source of contamination in a cleanroom. Therefore, rigorous training and ongoing testing of personnel are mandatory.

• Media-Fill Testing: This test simulates the most complex compounding procedure the personnel perform, but instead of using drugs, a microbial growth medium (soybean-casein digest medium) is used. The resulting preparation is incubated. If the broth turns cloudy (turbid), it indicates microbial growth, meaning the compounder failed the test. This must be performed initially, and then annually for low- and medium-risk compounding, or semi-annually (every 6 months) for high-risk compounding.
• Gloved Fingertip Testing: After garbing and before compounding, personnel press their gloved fingertips onto agar plates. The plates are incubated to check for colony-forming units (CFUs). Passing requires zero CFUs on both hands. This is performed at the same frequency as media-fill testing.

Environmental Monitoring

The cleanroom environment itself must be routinely monitored to ensure the engineering controls are functioning correctly.

• Air Sampling: Volumetric air sampling for viable microorganisms must be conducted at least every 6 months.
• Surface Sampling: Swabbing surfaces inside the PEC, Buffer Room, and Ante Room to culture for microorganisms must be conducted at least every 6 months.
• Temperature and Pressure: Room temperatures must be monitored daily (must be kept at 20°C or cooler). The pressure differential between the Buffer Room, Ante Room, and general pharmacy must be monitored daily or by a continuous monitoring system.

Hazardous Drug Handling (USP <800>)

Hazardous drugs pose a significant risk not only to the patient but to the healthcare workers handling them. These drugs include antineoplastics (chemotherapy), antiviral drugs, hormones, and some bioengineered drugs. The National Institute for Occupational Safety and Health (NIOSH) maintains a list of antineoplastic and other hazardous drugs used in healthcare.

USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings provides standards for the safe handling of these drugs to minimize occupational exposure.

Facility Requirements for Hazardous Drugs

Hazardous drugs cannot be compounded in the same environment as non-hazardous sterile drugs. They require specific engineering controls designed to contain the drug and exhaust it away from the worker.

• Negative Pressure: Both the C-PEC (Containment Primary Engineering Control, such as a Biological Safety Cabinet) and the C-SEC (Containment Secondary Engineering Control, the buffer room) must maintain negative pressure relative to adjacent areas. This ensures that if a door opens or a leak occurs, air flows into the hazardous room, preventing toxic aerosols from escaping into the rest of the pharmacy.
• External Exhaust: The air from the C-PEC and the C-SEC must be exhausted outdoors through HEPA filtration. It cannot be recirculated back into the facility.
• Storage: Hazardous drugs must be stored separately from non-hazardous drugs in a negative pressure room with external ventilation.

Personal Protective Equipment (PPE)

Handling hazardous drugs requires specialized PPE to protect the worker from dermal exposure and inhalation.

• Double Gloving: Two pairs of chemotherapy-tested gloves are required for compounding, administering, and disposing of hazardous drugs.
• Gowns: Disposable, impermeable gowns tested for resistance to chemotherapy drugs must be worn. They must close in the back and have long sleeves with elastic or knit closed cuffs.
• Eye and Face Protection: Required when there is a risk of splashing.
• Respiratory Protection: Required when unpacking hazardous drugs that are not contained in plastic, or when cleaning up a spill.

Closed-System Drug-Transfer Devices (CSTDs)

A CSTD is a specialized device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system. USP <800> states that CSTDs should be used when compounding hazardous drugs, and they must be used when administering antineoplastic hazardous drugs (e.g., by nurses). Using CSTDs adds a final, physical layer of protection to ensure that no toxic fumes or liquid drops breach the controlled environment, safeguarding healthcare workers who perform these critical tasks daily.