The United States Pharmacopeia (USP) General Chapter <797> outlines standards for Pharmaceutical Compounding – Sterile Preparations (CSPs) to ensure patient safety by minimizing risks of contamination, errors, and variability. The revised version, effective November 1, 2023, represents a major update from the 2008 edition, shifting from risk-level classifications (e.g., low-, medium-, high-risk) to a category-based system focused on compounding environment, controls, and validation. This guide provides accurate, detailed information on Beyond-Use Dates (BUDs), categories, storage, extensions, testing, environmental controls, personnel requirements, facility design, and compliance. It is based on the official USP <797> chapter and supporting resources from USP, ASHP, and other authoritative sources.

Key changes in the 2023 revision include:

• Elimination of risk levels in favor of Categories 1, 2, and 3.

• Emphasis on facility design, garbing, monitoring, and testing for longer BUDs.

• Updated BUD limits, with options for extensions via validation.

• Stricter requirements for nonsterile starting components, terminal sterilization, and multiple-dose preparations.

• Removal of references to hazardous drugs (now in <800>) and radiopharmaceuticals (in <825>).

• Allowance for validated alternative technologies if noninferior to standards.

This content prioritizes patient safety, regulatory compliance, and practical implementation.

Definitions and General Principles

A Beyond-Use Date (BUD) is the date or time after which a CSP must not be used, stored, transported, or administered, and must be discarded. It is determined from the date and time compounding is completed and must be shorter than or equal to the earliest expiration date of any ingredient or the chemical stability of the CSP. BUDs account for risks of microbial contamination, chemical degradation, and physical changes, ensuring the preparation remains safe and effective.

Key principles for assigning BUDs:

• Stability and Sterility: BUDs must be supported by stability-indicating data (e.g., from literature, studies, or monographs) and consider sterility risks. Use methods like high-performance liquid chromatography (HPLC) to confirm active ingredients remain within limits (e.g., 90–110% potency).

• Compounding Environment and Controls: Categories determine baseline BUDs, with extensions requiring enhanced monitoring, testing, and validation.

• Storage Conditions: Controlled room temperature (CRT: 20–25°C), refrigerated (2–8°C), or frozen (–25°C to –10°C). Colder storage generally extends BUDs but must not compromise stability.

• Starting Components: Sterile vs. nonsterile ingredients affect BUDs; nonsterile require sterilization (aseptic processing or terminal sterilization).

• Processing Method: Terminal sterilization (e.g., autoclaving, achieving <10⁻⁶ probability of nonsterility) allows longer BUDs than aseptic processing.

• Documentation: Maintain master formulation records (MFRs) for repeated CSPs and compounding records (CRs) for each batch, including ingredients, processes, BUD justification, and testing results. Records must be retrievable for at least 2 years.

• Immediate-Use CSPs: For urgent situations only; exempt from full <797> if prepared aseptically with ≤3 sterile products/ingredients, no hazardous drugs, and administered within 4 hours (or 1 hour if any nonsterile component). No storage or batch preparation allowed; personnel must be trained.

• Multiple-Dose CSPs: Must be Category 2 or 3. If preserved, discard after the shorter of the BUD or 28 days post-puncture/opening (supported by USP <51> antimicrobial effectiveness testing). Non-preserved aqueous (e.g., topical ophthalmic): discard 24 hours after opening at CRT or 72 hours refrigerated, for single-patient use only.

• Single-Dose Containers: After puncture in ISO Class 5 or better, discard remainders after 12 hours (or per manufacturer if shorter).

• Proprietary Bag/Vial Systems: BUD ≤ manufacturer's labeling; docking for activation ≤96 hours if not exceeding labeling.

• Allergenic Extracts: Specific exemptions; treated as CSPs but with adjusted garbing (no sterile outer garb) and BUDs if prepared in ISO Class 5 PEC.

BUDs must always be the shortest supported by all factors. If a USP-NF monograph exists for the CSP, follow its BUD if prepared accordingly (including testing).

Categories of CSPs

The 2023 revision replaces the old risk-level system with categories based on contamination risk, primarily determined by the compounding facility, environmental monitoring, garbing, disinfection frequency, and validation:

• Category 1 CSPs: Lowest controls; prepared in an unclassified Segregated Compounding Area (SCA) with an ISO Class 5 Primary Engineering Control (PEC, e.g., laminar airflow workbench or biological safety cabinet). Suitable for low-volume, short-storage needs. No cleanroom required, but SCA must be dedicated, with visible perimeter, temperature <20°C recommended, and hand hygiene station nearby (≥1m from PEC).

• Category 2 CSPs: Higher controls; prepared in a cleanroom suite (ISO Class 7 buffer room with ISO Class 8 ante-room) using aseptic processing or terminal sterilization. Allows longer BUDs with monthly monitoring and stability data. Can use sterile or nonsterile components (nonsterile must be sterilized).

• Category 3 CSPs: Highest controls for extended BUDs; also in a cleanroom suite, but requires batch-specific sterility testing, endotoxin testing (if applicable), weekly sporicidal disinfection, more frequent monitoring (e.g., monthly air, weekly surface), sterile outer garbing (no reuse without validation), and personnel qualifications every 3 months. Intended for high-volume or long-storage CSPs.

Differences from 2008: No more "risk levels" based on manipulations; focus on verifiable controls. Category 3 is not equivalent to old "high-risk" but enables longer BUDs with proof of low contamination risk.

Storage Conditions and Maximum BUD Limits

BUDs vary by category, starting components, processing method, storage, and testing. Assign the shortest BUD supported by stability data and sterility risks. Thaw frozen CSPs properly (e.g., at CRT or refrigerated) without exceeding total BUD. Tables below show maximum limits; actual BUDs may be shorter.

Maximum BUDs for Category 1 CSPs

(Prepared in SCA; no frozen storage allowed.)

Maximum BUDs for Category 2 CSPs

(Prepared in cleanroom; limits depend on components and method. No sterility testing required unless extending to tested limits.)

Maximum BUDs for Category 3 CSPs

(Requires sterility testing per batch; enhanced controls. Endotoxin testing for injectables from nonsterile components.)

Notes:

• For Category 3, BUD extensions require continuous compliance with all requirements (e.g., no deviations in monitoring).

• If using nonsterile components, ensure depyrogenation and filter integrity (0.22 μm filters).

• BUDs for lyophilized or alternative forms must be validated.

Requirements for Extended BUDs and Testing

Extending BUDs beyond defaults requires rigorous validation:

• Sterility Testing: Mandatory for all Category 3 CSPs and Category 2 CSPs extending to tested limits. Follow USP <71> (or validated alternative per <1223>). Batch size ≤250 units; sample per Table 3 in <71> (e.g., 10% for 1–39 units, rounded up). Test extra units if needed. No growth confirms sterility; failures require quarantine and investigation.

• Bacterial Endotoxin Testing: Required for injectable Category 2/3 CSPs from nonsterile components if BUD needs sterility testing; recommended otherwise. Per USP <85>.

• Stability Determination: Use stability-indicating methods to prove chemical/physical integrity to BUD end. Data from studies matching formula, process, and containers. Consider container-closure integrity (e.g., microbial ingress testing annually for Category 3).

• Antimicrobial Effectiveness: For preserved multiple-dose CSPs exceeding 28 days, pass USP <51>.

• Batch Limits and Documentation: Maximum 250 units for tested batches. Document all results, deviations, and corrective actions.

• Personnel and Facility Enhancements for Category 3: Every-3-month qualifications, sterile garbing (full coverage, no skin exposure), weekly sporicidal cleaning.

• Prohibitions: No extensions beyond table maxima, even with testing. Alternatives must be validated as noninferior.

Environmental Controls

• Facility Design: Category 1: Unclassified SCA with ISO 5 PEC, ≥20 air changes per hour (ACPH), humidity <60%. Category 2/3: Cleanroom suite with ISO 5 PEC in ISO 7 buffer (≥30 ACPH, positive pressure ≥0.02 inches water column), ISO 8 ante-room (≥20 ACPH). HEPA filters, continuous pressure monitoring, low-wall returns. No exceptions for isolators in unclassified areas.

• Monitoring: Nonviable particles every 6 months; viable air sampling every 6 months (Category 1/2) or monthly (Category 3); surface sampling monthly (1/2) or weekly (3). Action levels: >1 CFU in ISO 5 air, >3 CFU surface ISO 5. Identify microbes to genus if exceeded; remediate (e.g., for gram-negative rods).

• Cleaning and Disinfection: Daily with EPA-registered agents; monthly sporicidal (weekly for Category 3 floors/walls). Sterile 70% IPA in PEC every 30 minutes during continuous compounding.

• Certification: PEC and rooms certified every 6 months; dynamic airflow smoke studies.

Personnel Training, Qualifications, and Garbing

• Designated Person: Oversees compliance, training, and quality assurance.

• Training: Initial didactic and competency for all; ongoing every 12 months. Aseptic technique, garbing, and media-fill testing every 6 months (Category 1/2) or 3 months (Category 3).

• Garbing: Low-lint, sterile gloves; full garb (gown, mask, hair/beard covers) in buffer areas. For Category 3: Sterile outer garb, no reuse. Hand hygiene: Wash with soap, then alcohol-based sanitizer.

• Competency: Initial 3 successful garbing/gloved fingertip samplings; media-fills simulate worst-case scenarios.

Compliance, Quality Assurance, and Benefits

• Compliance: Align with USP <797>, state boards, FDA (for outsourcing facilities), and accreditation (e.g., Joint Commission). Conduct internal audits, maintain SOPs, and have recall procedures for out-of-spec CSPs.

• Quality Assurance: Visual inspections pre-release; investigate complaints/deviations. Redispensing allowed only if integrity maintained.

• Benefits: Reduced contamination (e.g., microbial lag phase minimized via testing), improved patient outcomes, cost savings from extended BUDs, and regulatory alignment. Studies show enhanced controls lower infection risks in healthcare settings.

• Resources: USP Compounding Compendium, ASHP guidelines, FDA compounding page. For tools/software, consider compliant platforms for tracking and documentation.

Implementation Steps for USP <797> BUD Standards

Implementing the revised USP <797> (effective November 1, 2023) requires integrating category-based standards (Categories 1, 2, and 3) with state regulations, pharmacist oversight, training, and continuous improvement. Focus on facility controls, monitoring, and validation for safe BUD assignment. Designate a compounding supervisor for oversight and use a phased approach: assessment, planning, training, execution, and monitoring.

1. Aligning with State Rules and Regulations

State boards may add requirements like extra monitoring or documentation. As of December 2025, most states align with USP, but check for variations (e.g., California's facility certifications or Washington's annual self-inspections).

Steps:

• Audit state laws via NABP or board websites.

• Update SOPs for specifics (e.g., quarterly sampling if required).

• Maintain a compliance calendar for reports and inspections.

• Use tools like Simplifi 797 for alerts.

Harmonize to avoid fines and ensure defensibility.

2. Pharmacist Decision Making in Assigning BUDs

Pharmacists assign BUDs based on stability, category, environment, and processing, using the shortest supported limit.

Key Factors:

• Ingredient stability (e.g., studies via USP-NF).

• Storage and containers (e.g., integrity testing).

• Category and method (e.g., aseptic vs. terminal sterilization).

• Monitoring results (e.g., adjust for CFU exceedances).

• Sterility protocols (e.g., testing for extensions).

Process:

1. Gather data from MFRs/CRs.

2. Assess risks with checklists.

3. Assign and document BUD.

4. Review per batch.

Use software for calculations; thorough records protect against audits.

3. Training Resources and Programs

Training ensures competency in aseptic techniques and BUDs, with frequencies by category (every 6 months for 1/2, 3 months for 3).

Build Programs:

• Include hygiene, garbing, media-fills, and assessments.

• Use platforms: CompoundLearn, USP eLearning, ASHP videos.

• Customize for roles; track with LMS such as CompoundLearn

4. Expanding Your Knowledge and Continuous Improvement

Stay updated via USP alerts, ASHP guidelines, and networks.

Focus Areas:

• Monitoring: Real-time tools and remediation.

• Documentation: Digital systems for traceability.

• Assessment: Stability testing and cases.

Strategies:

• Join APhA/ASHP for webinars.

• Use CompoundLearn for compounding training materials, videos, case studies

• Roadmap: Gap analysis, phased rollout, quarterly reviews.

This fosters innovation, like safe BUD extensions to cut waste. Subscribe to updates for ongoing compliance.

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