USP 797 Risk Levels Explained
May 1, 2025
USP 797 sets the standards for sterile compounding in U.S. pharmacies to ensure safety and quality. The 2023 update introduced a new category-based system - Categories 1, 2, and 3 - replacing the older low, medium, and high-risk levels. Here's a quick breakdown:
Category 1: Basic setups with ≤12-hour beyond-use dating (BUD) and monthly air sampling.
Category 2: ISO Class 7 cleanrooms with ≤30-hour BUD and weekly monitoring.
Category 3: ISO Class 5 environments with up to 180-day BUD, sterility testing, and stricter controls.
Key Differences:
Stricter environmental controls and monitoring as categories increase.
Higher staff competency requirements for advanced categories.
Clear guidelines for contamination prevention and compliance.
This update ensures pharmacies align contamination risks with proper controls for patient safety.
New guidelines for sterile compounding.
USP 797 Risk Level Categories
The 2023 update to USP 797 introduced a category-based system, replacing the older low, medium, and high-risk designations. This new approach - using Categories 1, 2, and 3 - focuses on environmental controls and contamination risks rather than procedural complexity.
Changes in Risk Level Classification
Switching to this category-based system addresses previous inconsistencies in risk assessment. For instance, a 2021 survey found that 42% of compounding pharmacies misclassified batch preparations as low-risk under the old system. The updated framework provides clearer, more objective guidelines.
Category | Environment Required | Beyond-Use Dating | Key Requirements |
|---|---|---|---|
Category 1 | Segregated Compounding Area | ≤12 hours | 30 ACH, monthly air sampling (threshold ≤3 CFU/m³) |
Category 2 | ISO Class 7 cleanroom | ≤30 hours | Enhanced air sampling, cleanroom suite |
Category 3 | ISO Class 5 environment | Up to 180 days | Sterility testing, full barrier systems |
The table above highlights the main features of each category. Below, we break down the detailed criteria used for classification.
Risk Level Assessment Criteria
The new system evaluates sterile compounding risks based on several critical factors:
Environmental Controls
Requirements vary by category, from basic Segregated Compounding Areas to ISO Class 5 environments. For example, Category 3 facilities must maintain ISO Class 5 conditions with 45 ACH and weekly air sampling (threshold ≤1 CFU/m³). In contrast, Category 1 requires 30 ACH and monthly air sampling (threshold ≤3 CFU/m³).
Monitoring Requirements
Environmental monitoring becomes stricter as risk increases. Category 1 areas require monthly air sampling (threshold ≤3 CFU/m³), while Category 3 areas demand weekly sampling (threshold ≤1 CFU/m³).
Personnel Requirements
Staff competency standards rise with each category. For example, Category 3 operations mandate quarterly media-fill testing to verify aseptic techniques, whereas Category 1 only requires annual validation.
Surface Sampling
Action levels for contamination decrease with higher risk. Category 1 allows up to 5 CFU/plate, while Category 3 limits this to 1 CFU/plate.
This updated classification system offers a more structured and precise approach to sterile compounding. By aligning controls with contamination risks, pharmacies can better ensure product safety and meet regulatory standards.
Risk Levels in Detail
This section outlines the requirements for Category 1 (low-risk) sterile compounding under the updated USP 797 guidelines. These requirements focus on maintaining safety and sterility during the compounding process.
Low-Risk Level Requirements
Environmental Standards
A segregated compounding area (SCA) with controlled temperature.
At least 30 air changes per hour (ACH).
An environment that meets or surpasses ISO Class 7 standards.
Unidirectional airflow to maintain sterility.
Operational Parameters
Single transfers of sterile products.
Minimal handling or manipulation of products.
Use of basic aseptic techniques.
Beyond-use date (BUD) limited to 12 hours at room temperature.
Examples of Low-Risk Preparations
Single-dose antibiotic syringes.
Patient-specific eye drops.
Simple IV fluid additions.
Pharmacy Practice Requirements
USP 797 risk levels play a key role in shaping pharmacy operations, setting the standards for both facilities and staff protocols.
Facility and Testing Standards
Primary engineering controls (PEC) must meet ISO Class 5 conditions across all risk levels. Surrounding areas have stricter requirements as the risk classification increases.
Area Type | Low-Risk | Medium-Risk | High-Risk |
|---|---|---|---|
Buffer Room | ISO 7 | ISO 7 | ISO 7 |
Ante-Room | Optional | ISO 8 | ISO 7 |
Pressure Differential | ≥0.02" WC | ≥0.02" WC | ≥0.04" WC |
Air Changes/Hour | 30 | 30 | 60 |
These standards are closely tied to rigorous testing protocols to ensure sterility in compounding. Facilities must maintain a temperature of ≤68°F (20°C) and relative humidity of ≤60%.
Key Testing Requirements:
Low-Risk: Visual inspection of final products
Medium-Risk: Sterility testing on 10% of batches using membrane filtration
High-Risk: Sterility testing on all batches, plus bacterial endotoxin testing
Staff Training and Documentation
In addition to facility standards, staff training is crucial for maintaining compliance. Training programs are tailored to the facility's risk classification.
Main Training Elements:
Initial classroom-based training
Written competency tests
Gloved fingertip sampling
Aseptic technique assessments
Media fill testing
For high-risk compounding, training must occur every six months and include procedures for handling hazardous drugs and working in negative pressure environments.
Documentation Requirements:
Risk Level | Retention Period | Required Documentation |
|---|---|---|
Low-Risk | 1 year | Basic compounding records |
Medium-Risk | 3 years | Master formulation records |
High-Risk | 5 years | Full traceability documentation |
Facility managers are responsible for keeping records on environmental monitoring, equipment calibration, staff certifications, cleaning schedules, and pressure readings. High-risk facilities must also use automated systems to continuously monitor environmental conditions.
Risk Level Quick Reference
The 2023 USP 797 updates shift the framework from traditional risk levels to a category-based system, focusing on measurable environmental controls rather than process complexity.
Here’s a summary of the key requirements:
Comparison Chart
Core Requirements Across Categories:
Requirement | Category 1 | Category 2 | Category 3 |
|---|---|---|---|
Beyond-Use Dating | Limited per guidelines | Limited per guidelines | Up to 180 days with validation |
Air Quality | ISO 8 PEC with ISO 7 buffer area | ISO 7 PEC with ISO 7 anteroom | ISO 5 PEC within ISO 7 cleanroom |
Environmental Monitoring | Monthly viable air sampling | Weekly viable air sampling | Daily particle monitoring |
Personnel Testing | Annual media fills | Semi-annual media fills + endotoxin testing | Quarterly media fills + batch testing |
Critical Control Points
The chart above highlights the increasing requirements across categories. Category 1 involves basic transfers and reconstitutions using commercially available products, with limited environmental monitoring.
Category 2 introduces stricter controls, including documented personnel competency for routine sterile compounding tasks.
"503Pharma emphasizes that 90% of facility non-compliance issues stem from inadequate airflow validation in high-risk settings."
Category 3, the highest level, requires the most stringent measures, such as:
Continuous particle monitoring systems
Quarterly media fills with batch testing
Zero CFU action level for surface sampling
Detailed batch-specific documentation
Enhanced pressure differential monitoring (≥0.04" WC)
Key Compliance Metrics
For Category 3, maintaining measurable environmental controls is crucial. Facilities must adhere to strict standards, including:
Maintaining 6 ACH in ante-areas
These metrics reflect USP 797's emphasis on clear, measurable standards to help compounding facilities achieve compliance.
Summary
The 2023 USP 797 updates have introduced new standards for managing risks in sterile compounding. Adopting these changes requires accuracy and reliable tools.
For compounding pharmacies aiming to meet these updated standards, 503Pharma provides validated formulas and educational materials to help simplify processes while adhering to the new category-based system.
Key points for staying compliant under the revised framework include:
Environmental Controls: Focus on measurable factors like air changes per hour and pressure differentials to maintain proper conditions.
Recordkeeping: Stricter rules for batch-specific records and verifying staff competency.
Testing Protocols: Regular environmental checks based on the specific category requirements.
Beyond-Use Dating: Category-based limits that impact workflow and inventory planning.
These updates emphasize clear, measurable standards designed to improve quality and consistency in sterile compounding.
The shift to more objective standards not only ensures better quality control but also supports smoother pharmacy operations. Pharmacies can access educational tools to stay updated on best practices and compliance needs.
FAQs
What are the key differences between the updated USP 797 categories and the previous low, medium, and high-risk levels?
The updated USP 797 guidelines replace the previous low, medium, and high-risk levels with a category-based system that focuses on two main classifications: Category 1 and Category 2. These categories are designed to simplify risk assessment and emphasize the conditions under which sterile preparations are compounded, stored, and used.
Category 1: Preparations have shorter beyond-use dates (BUDs) and are typically compounded in less controlled environments, such as segregated compounding areas.
Category 2: Preparations have longer BUDs and require stricter environmental controls, such as ISO Class 7 cleanrooms.
This new system aims to streamline compliance while maintaining patient safety. For more detailed insights into USP 797 updates and their implications for sterile compounding, educational platforms like 503Pharma can provide valuable resources and guidance.
What are the environmental monitoring requirements for each risk category under the updated USP 797 guidelines?
Under the updated USP 797 guidelines, environmental monitoring requirements become more stringent as the compounding risk level increases. Category 1 has the least intensive requirements, as it involves shorter beyond-use dates and less complex sterile compounding. Category 2 introduces more rigorous monitoring standards to ensure sterility for products with longer beyond-use dates or more complex preparation. Category 3, the highest risk level, demands the most comprehensive environmental controls and monitoring to maintain sterility for high-risk preparations.
These requirements are designed to mitigate contamination risks and ensure patient safety, with each category tailored to the specific complexities and risks of sterile compounding activities.
What training and documentation are required for pharmacy staff to meet the updated USP 797 standards?
To comply with the updated USP 797 standards, pharmacy staff must complete specific training and maintain proper documentation to ensure compliance and patient safety. Training should cover sterile compounding techniques, aseptic practices, and proper use of personal protective equipment (PPE). Regular competency assessments are also required to verify skills and adherence to protocols.
Documentation must include detailed records of training sessions, competency evaluations, and standard operating procedures (SOPs). Additionally, pharmacies need to maintain logs for environmental monitoring, cleaning schedules, and any deviations or corrective actions. Consistent and accurate documentation is critical for regulatory compliance and quality assurance.