26 Sterility and Cleanliness Requirements

While non-sterile compounding does not require sterility, it must adhere to rigorous standards for hygiene, contamination control, and environmental conditions to prevent errors and protect both patients and personnel. Compounded products that are contaminated or improperly handled can lead to therapeutic failure, adverse events, or exposure to hazardous substances.  The NAPRA Model Standards for Pharmacy Compounding of Non-Sterile Preparations outlines specific requirements to support environmental control, including designated compounding areas, appropriate engineering controls for hazardous preparations, scheduled cleaning and disinfection routines, personal protective equipment (PPE) use, and environmental monitoring practices. This chapter provides a comprehensive overview of these standards, emphasizing practical implementation strategies and documentation expectations within the pharmacy setting.

Cleanliness & Environmental Control in Non-Sterile Compounding

1. Designated Compounding Areas

• Separate and dedicated spaces must be used for non-sterile compounding to prevent cross-contamination.
• Hazardous and non-hazardous compounding must be physically separated.
• Compounding must not occur in areas where:
  • Eating or drinking occurs
  • Waste is processed
  • Foot traffic is high

2. Cleaning and Disinfection Protocols

NAPRA requires routine and documented cleaning procedures for the compounding environment.

Cleaning and Disinfection Protocols:

**NAPRA requires written procedures for all cleaning protocols and a log to record each cleaning activity.

3. Personal Hygiene and PPE

• Hand hygiene is mandatory before entering the compounding area and before donning PPE.
• No jewelry, nail polish, or cosmetics allowed.
• Clean lab coats or gowns must be worn; change as needed (e.g., between different types of products).
• For hazardous non-sterile compounding, PPE must meet Section 9.2.3 of NAPRA, including:
  • Two pairs of chemotherapy-rated gloves (ASTM D6978)
  • Gowns with chemical resistance (polyethylene-coated)
  • Head/hair/shoe covers
  • Eye/face protection
  • Respiratory protection (e.g., N95 or full-face respirator) when needed

4. Environmental Controls

• Temperature and humidity must be monitored and maintained within acceptable ranges (as defined by monographs or product needs).
• Ventilation must ensure adequate air exchanges, especially in areas where hazardous ingredients are handled.

Hazardous non-sterile compounding must occur in a C-PEC located within a C-SEC (Containment Secondary Engineering Control) that meets ventilation standards.

5. Documentation and Quality Assurance

• NAPRA mandates a comprehensive QA program with:
  • Standard Operating Procedures (SOPs)
  • Cleaning logs
  • Equipment maintenance records
  • Environmental monitoring logs
    • particulate matter, airflow direction in C-PECs, humidity thresholds, especially for Level B or C risk
  • Incident and deviation reports
    • NAPRA encourages pharmacies to have SOPs in place for handling spills, including for hazardous ingredients

Cleanliness and environmental control are foundational elements of safe and effective non-sterile compounding. By following NAPRA’s requirements for designated compounding spaces, routine cleaning and disinfection, proper PPE use, and environmental monitoring, pharmacy teams can significantly reduce the risk of contamination. Documentation and quality assurance activities further support compliance and accountability. Through consistent adherence to these best practices, compounding personnel help ensure that every preparation meets its intended quality standards while maintaining a safe and hygienic work environment.