6.2 Hazardous Drug Handling and USP <800> Compliance in Nonsterile Compounding
Key Takeaways
- The NIOSH 2024 hazardous-drug list uses two tables; reproductive and developmental hazards are identified within them rather than in an obsolete third group.
- Nonsterile HD compounding occurs in a C-PEC inside a separate externally vented C-SEC at 0.01–0.03 inch water column negative pressure and at least 12 ACPH; room exhaust need not be HEPA-filtered.
- HD compounding PPE includes two ASTM D6978 glove pairs, an HD-resistant gown, head/hair covers, and two shoe-cover pairs; respiratory and eye/face protection follow activity risk and never replace containment.
- HD surfaces require deactivation, decontamination, and cleaning; disinfection is added when sterile compounding requires it, not universally for nonsterile work.
- Wipe sampling initially and at least every six months and medical surveillance are recommended controls; findings drive documented investigation and corrective action.
6.2 Hazardous Drug Handling and USP <800>
Quick Answer: Identify hazardous drugs with the current NIOSH List and the entity-specific HD list. Nonsterile HD compounding occurs in a C-PEC within a separate externally vented C-SEC maintained at 0.01–0.03 inch water column negative pressure and at least 12 ACPH. PPE complements containment; it never authorizes powdered-HD manipulation outside the required C-PEC.
Current NIOSH Framework
The NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 superseded the 2016 list. The current list uses two tables:
| Table | Meaning |
|---|---|
| Table 1 | Drugs whose manufacturer labeling contains special handling information |
| Table 2 | Drugs that meet one or more NIOSH hazardous-drug criteria but lack that labeling |
Developmental and reproductive hazards are identified within those tables; there is no current separate “Group 3” table. The entity maintains an HD list that includes the drugs and dosage forms it handles and uses the current NIOSH list plus manufacturer information and later notices.
A drug can be hazardous because of carcinogenicity, developmental or reproductive toxicity, genotoxicity, organ toxicity at low doses, or a structure/toxicity profile similar to an existing HD. Risk controls consider formulation and activity: an intact coated tablet may present a different exposure risk than crushing that tablet into airborne powder.
Engineering Controls
C-PEC: Where Nonsterile HD Compounding Occurs
Powder-generating nonsterile HD compounding must occur in a Containment Primary Engineering Control (C-PEC), such as a suitable containment ventilated enclosure or Class I/II biological safety cabinet. A closed-system processing device may reduce exposure for a non-HD process evaluation, but it is not automatically a substitute for an <800>-required C-PEC.
For nonsterile compounding, external venting of the C-PEC is preferred. The chapter permits the specified alternative of two redundant HEPA filters in series when the unit and facility design meet the requirements. Personnel follow certification, operation, cleaning, and maintenance instructions for the exact device.
C-SEC: The Containment Room
The C-PEC is located in a Containment Secondary Engineering Control (C-SEC) that is:
- a separate room;
- externally vented;
- maintained at 0.01–0.03 inch water column negative pressure to adjacent areas; and
- supplied with at least 12 air changes per hour.
USP <800> does not require HEPA filtration of the room exhaust. Pressure is continuously monitored so a loss of containment can be detected and addressed.
PPE for Nonsterile HD Compounding
For compounding, <800> specifies two pairs of chemotherapy gloves tested to ASTM D6978, an HD-resistant gown, head/hair covers, and two pairs of shoe covers. Place the second shoe-cover pair before entering the C-SEC and remove it when exiting as the entity SOP directs.
Eye/face and respiratory protection depend on the activity and exposure risk. A fit-tested N95 may be part of an OSHA-compliant respiratory-protection program for particle exposure; a PAPR may be selected where appropriate. A surgical mask does not protect against HD aerosols. Most importantly, a respirator is not permission to crush or weigh powdered HDs outside a C-PEC.
Personnel receive initial HD training and demonstrate competency before handling HDs, then at least every 12 months and when new hazards or duties are introduced.
Receipt, Storage, Transport, and Spill Control
- Inspect incoming HD packages for damage in an area that limits exposure; do not open a visibly damaged package in routine space.
- Store HDs separately from non-HDs and prevent breakage, leakage, and unauthorized access.
- Use sealed, labeled, leak-resistant transport containers.
- Keep a spill kit readily available and restrict cleanup to trained personnel wearing PPE selected for the spill.
- Dispose of HD waste through the entity's hazardous-waste program; do not place trace or bulk HD waste into ordinary trash.
Surface and Equipment Control
Areas and equipment that contact HDs undergo:
- Deactivation—render the HD less hazardous when a suitable agent exists;
- Decontamination—remove HD residue;
- Cleaning—remove organic and inorganic material.
Disinfection is an additional step when sterile compounding requires microbial control. It is not a universal fourth step for nonsterile HD compounding. Select agents from compatibility and HD-specific information; bleach, peroxide, alcohol, or a commercial product is not interchangeable for every drug and surface.
Equipment that directly contacts an HD should be dedicated when possible or subjected to an evaluated decontamination process before other use. Prevent transfer of residue to handles, pens, phones, packaging, or non-HD work areas.
Wipe Sampling and Medical Surveillance
USP <800> states that surface wipe sampling should be performed initially and at least every six months, or more often when warranted. It is a recommended assessment tool rather than a blanket “must.” If residue is found, review handling, cleaning, traffic, and engineering controls and document corrective actions.
A medical-surveillance program is recommended for workers who handle HDs. The occupational-health program uses exposure history, symptoms, reproductive considerations, and follow-up defined by risk and applicable OSHA/employer requirements; <800> does not prescribe a universal CBC and chemistry-panel schedule for every worker.
Exam Decision Pattern
If an HD powder is being crushed, weighed, or mixed outside containment, stop the task and move it into the required C-PEC. Do not choose “add an N95 and continue.” If a question asks about the current NIOSH structure, choose the 2024 two-table framework.
Under USP Chapter <800>, what is the mandatory pressure differential requirement for a nonsterile Containment Secondary Engineering Control (C-SEC)?
Which testing standard must gloves meet to be deemed compliant for hazardous drug compounding under USP <800>?
Which sequence identifies the core USP <800> surface processes for nonsterile HD compounding?
A technician is about to crush spironolactone tablets for a compounded suspension outside the required containment device. What is the correct response?