Sterile Compounding Deep Dive
Sterile compounding is the preparation of medications that must be free from microbial contamination, such as intravenous solutions, injections, and ophthalmic preparations. USP Chapter 797 sets the standards for compounded sterile preparations (CSPs). This topic is heavily tested on the CPHT exam.
When Is Sterile Compounding Required?
Any preparation intended for the following routes must be sterile:
- Intravenous (IV)
- Intramuscular (IM)
- Subcutaneous (SubQ)
- Intrathecal
- Ophthalmic (eye preparations)
- Inhalation (certain preparations)
- Any route that bypasses the body's natural defenses
Cleanroom Design and ISO Classifications
Sterile compounding environments are classified by the maximum number of airborne particles per cubic meter of air. Lower ISO numbers mean cleaner air.
| ISO Class | Maximum Particles (0.5 micron or larger) per cubic meter | Where Used |
|---|---|---|
| ISO Class 5 | 3,520 | Inside the PEC (LAFW, BSC, or CAI) - the direct compounding area |
| ISO Class 7 | 352,000 | Buffer area (cleanroom) surrounding the PEC |
| ISO Class 8 | 3,520,000 | Ante-area (where garbing occurs) |
Engineering Controls
- PEC (Primary Engineering Control): The device that provides ISO Class 5 air for compounding.
- LAFW (Laminar Airflow Workbench) - Horizontal: HEPA-filtered air flows horizontally from the back of the hood toward the compounder. Used for non-hazardous sterile compounding.
- LAFW - Vertical: HEPA-filtered air flows downward. Also used for non-hazardous work.
- BSC (Biological Safety Cabinet): Used for hazardous drugs. Provides both product and personnel protection.
- CAI/CACI (Compounding Aseptic Isolator / Containment Aseptic Containment Isolator): Enclosed units that provide ISO Class 5 conditions.
- SEC (Secondary Engineering Control): The room in which the PEC is placed (buffer area and ante-area).
Aseptic Technique Fundamentals
Aseptic technique is the set of practices used to prevent microbial contamination during sterile compounding.
Critical Site
Any opening or surface that comes into direct contact with the sterile product or the path between the product and the environment. Examples include needle tips, syringe tips, vial tops (after swabbing), and IV port openings. Critical sites must never be touched, breathed on, or placed between the HEPA filter and the product.
First Air
The air that comes directly from the HEPA filter before it passes over any object. Critical sites should always be in the path of first air. Never place objects between the HEPA filter and critical sites.
Working in the Hood
- Work at least 6 inches inside the outer edge of the hood.
- Do not block airflow vents or place objects on the side-wall intake grilles.
- Keep materials arranged so that smaller items are closest to the HEPA filter and larger items are downstream.
- Never cough, sneeze, or talk directly into the hood.
- Wipe all surfaces and items with sterile 70% isopropyl alcohol (IPA) before placing them in the PEC.
- Allow IPA to dry completely before beginning compounding (wet IPA can contaminate the preparation).
Garbing Procedure
Garbing must follow a specific order to minimize contamination. The general order is:
- Remove outer garments and personal items (jewelry, watches).
- Don shoe covers (in the ante-area).
- Don hair cover (and beard cover if applicable).
- Don face mask.
- Perform hand hygiene: wash hands and forearms up to the elbows with antimicrobial soap for at least 30 seconds.
- Dry hands with low-lint towels.
- Don non-shedding gown.
- Apply alcohol-based hand rub and allow to dry.
- Don sterile gloves (at the line of demarcation or inside the buffer area).
- Sanitize gloves with sterile 70% IPA.
Gloves must be sanitized with sterile 70% IPA frequently during compounding, especially after touching non-sterile surfaces.
Environmental Monitoring
USP 797 requires ongoing environmental monitoring to ensure the compounding environment meets standards:
- Viable air sampling: Tests for living microorganisms in the air.
- Viable surface sampling: Tests surfaces for microbial contamination using contact plates or swabs.
- Nonviable particle counting: Measures total airborne particles (regardless of viability) to verify ISO classification.
- Temperature and humidity monitoring: The buffer area should generally be maintained at a controlled room temperature with humidity levels that do not promote microbial growth.
Personnel Competency
All personnel performing sterile compounding must demonstrate competency through:
- Didactic training: Classroom or online education on aseptic technique principles.
- Practical (hands-on) training: Supervised practice in the cleanroom.
- Media-fill testing: A simulation where the compounder prepares a CSP using growth media (such as trypticase soy broth) instead of actual drug. The media is then incubated to check for microbial growth. Growth indicates a failure in aseptic technique.
- Gloved fingertip sampling: After garbing, the compounder touches agar plates with gloved fingertips to test for contamination.
- Competency must be demonstrated initially and on an ongoing basis (frequency per facility policy and USP 797 requirements).
Beyond-Use Dating (BUD)
The BUD is the date and time after which a CSP should not be used. BUD depends on the risk level of the preparation, storage conditions, and whether sterility testing has been performed. USP 797 provides default BUD assignments in the absence of stability data. Because USP 797 has been revised and the specific default BUD tables may change with revisions, consult the current version of USP 797 for exact BUD assignments.
Key principles:
- Shorter BUDs are assigned to preparations with higher contamination risk.
- Preparations stored at controlled room temperature generally have shorter BUDs than those stored under refrigeration or frozen.
- Sterility testing can support extended BUDs.
- The BUD must never exceed the earliest expiration date of any ingredient used in the CSP.
Common Sterile Compounding Tasks
- Reconstituting lyophilized (freeze-dried) medications with appropriate diluent
- Preparing IV admixtures (adding drugs to IV bags)
- Preparing total parenteral nutrition (TPN) solutions
- Preparing chemotherapy agents (in a BSC)
- Preparing ophthalmic solutions
- Preparing syringes for injection
Cleaning and Disinfection
- The PEC interior should be cleaned with sterile 70% IPA before each batch and after any spill.
- Counters and surfaces in the buffer and ante-areas should be cleaned regularly with appropriate disinfectants.
- Floors should be mopped; walls and ceilings should be cleaned on a scheduled basis.
- A sporicidal agent should be used periodically in addition to 70% IPA.
Exam Tips
- Know the ISO classifications: ISO 5 for the PEC, ISO 7 for the buffer area, ISO 8 for the ante-area.
- Understand the garbing order - this is frequently tested.
- Know what "first air" and "critical site" mean and why they matter.
- A horizontal LAFW is for non-hazardous drugs; a BSC is for hazardous drugs.
- Media-fill testing checks the compounder's aseptic technique, not the product itself.
- USP 797 governs sterile compounding; USP 795 governs non-sterile compounding; USP 800 governs hazardous drug handling.