Introduction

The United States Pharmacopeia (USP) General Chapter <797> establishes essential standards for compounding sterile preparations (CSPs) in pharmacies and healthcare settings to minimize contamination risks and ensure patient safety. The chapter underwent a significant revision that became official on November 1, 2023, shifting from the outdated low-, medium-, and high-risk level system to a more objective, category-based framework (Categories 1, 2, and 3). This update emphasizes environmental controls, beyond-use dates (BUDs), and verifiable processes rather than procedural complexity, addressing inconsistencies in prior classifications and enhancing compliance.

This post provides a comprehensive overview of the updated system, drawing from official USP sources, to help compounding professionals navigate compliance effectively.

Categories

The 2023 revision introduces three categories based on compounding conditions and potential contamination risk, replacing the subjective risk-level system:

• Category 1: For CSPs with the lowest risk, compounded in an SCA or cleanroom with limited manipulations. Suitable for simple preparations like reconstituting single-dose vials.

• Category 2: For CSPs requiring higher controls, compounded in a cleanroom suite (ISO Class 7 buffer with ISO Class 8 ante-area). Allows for longer BUDs and more complex processes.

• Category 3: For high-risk CSPs needing extended BUDs, compounded in a cleanroom with additional safeguards like sterility testing for batches. Ideal for large-scale or long-storage preparations.

Categorization depends on factors such as the number of manipulations, use of sterile vs. nonsterile components, and environmental quality, ensuring objective assessment.

Storage Conditions

Storage must maintain CSP integrity:

• Controlled Room Temperature (CRT): 20°C–25°C, with excursions up to 30°C not exceeding 24 hours cumulatively.

• Refrigeration: 2°C–8°C, avoiding freezing unless validated.

• Freezing: -25°C to -10°C for extended stability.

• Hazardous Drugs: Follow USP <800> for segregated storage to prevent cross-contamination.

All storage areas require continuous monitoring with alerts for deviations, and CSPs must be labeled with specific storage instructions.

BUD Limits

BUDs are assigned based on category, formulation type, and storage conditions. The following tables summarize default limits (without extensions):

Aseptically Processed CSPs (No Sterility Testing)

Terminally Sterilized CSPs

BUDs assume proper aseptic technique and validated stability; shorter BUDs apply if stability data indicate otherwise.

Requirements for Extensions and Testing

Extensions beyond default BUDs require rigorous validation:

• Sterility Testing: Mandatory for Category 3 batches >25 units or extended BUDs. Use methods like membrane filtration or direct inoculation per USP <71>.

• Stability Studies: Conduct chemical and physical testing (e.g., pH, potency) to support extensions.

• Endotoxin Testing: Required for Category 3 non-intrathecal CSPs using methods from USP <85>.

• Documentation: Maintain records of testing results, with release only after passing criteria (e.g., no growth in sterility tests).

Facilities must have written procedures for testing, and extensions are not permitted for Category 1.

Environmental Controls

Environmental quality is critical:

• Nonviable Particle Monitoring: Certify PECs and cleanrooms semiannually (ISO 5: ≤3,520 particles ≥0.5 μm/m³).

• Viable Air Sampling:

  • Category 1: Monthly.

  • Category 2: Weekly in PEC, monthly in buffer/ante.

  • Category 3: Daily in PEC during compounding.

• Surface Sampling: Weekly for Category 3 PECs; monthly for others. Action levels: ≤3 CFU for ISO 5, ≤5 for ISO 7.

• Pressure Differentials: Positive pressure (≥0.02 inches water column) in non-hazardous areas.

• Cleaning: Daily for PECs using sterile 70% IPA; monthly deep cleans with sporicidal agents.

Monitoring data must be reviewed promptly, with corrective actions for excursions.

Personnel Training, Qualifications, and Garbing

Personnel must demonstrate competency:

• Training: Didactic instruction, written tests, and hands-on assessments covering aseptic technique, cleaning, and USP standards.

• Qualifications: Initial and ongoing (annual for Category 1/2, semiannual for Category 3) via media-fill tests and gloved fingertip sampling (≤0 CFU initially, ≤3 CFU ongoing).

• Garbing:

  • Hand hygiene: Wash with soap, then alcohol-based sanitizer.

  • Sequence: Shoe covers, head/beard covers, face mask, gown, sterile gloves.

  • No jewelry, makeup, or artificial nails; garbing in ante-area.

Requalification required after failures or extended absences.

Compliance and Quality Assurance

Compliance involves:

• Standard Operating Procedures (SOPs): For all processes, reviewed annually.

• Master Formulation Records: Detail ingredients, procedures, and BUDs.

• Audits and Inspections: Internal reviews and readiness for FDA/state board inspections.

• Quality Assurance Program: Includes complaint handling, adverse event reporting, and trend analysis of monitoring data.

FDA enforces USP <797> under compounding laws, with non-compliance risking warnings or shutdowns.

Implementation Steps

Alignment with State Rules

While USP <797> sets federal baselines, states may impose variations. Pharmacies must review board of pharmacy regulations for full compliance. Examples include:

Consult your state board for tailored guidance.

Pharmacist Decision-Making

Pharmacists play a pivotal role in category assignment and compliance. Follow this process outline:

1. Assess Preparation: Evaluate components, manipulations, and intended use to determine category (e.g., simple vial transfer = Category 1).

2. Review Stability Data: Assign BUD based on validated studies or defaults.

3. Verify Controls: Ensure environmental, personnel, and testing requirements are met.

4. Document and Release: Record decisions in compounding logs; only release after quality checks.

5. Monitor and Adjust: Review trends and update SOPs as needed.

This structured approach ensures informed, safety-focused decisions.

Training Resources and Programs

Effective training is vital for compliance. Consider these resources:

Incorporate a mix for comprehensive staff development.

Expanding Knowledge and Continuous Improvement

To stay ahead, pharmacies should foster ongoing learning:

• Participate in professional organizations like ASHP or NABP for updates.

• Conduct internal audits and mock inspections quarterly.

• Use tools like CompoundLearn for case studies, simulation tools, and aids in implementing USP <797> practically—its tailored content helps with real-world scenarios like BUD extensions.

• Attend annual conferences or subscribe to USP alerts for errata.

Continuous improvement not only ensures compliance but also enhances operational resilience and patient outcomes.

Related posts

• USP 797 vs USP 800: Key Differences Explained

• How to Design an Efficient Sterile Compounding Workflow

• USP 797 BUD Standards Explained

• USP 797 Immediate-Use Rules Explained