Cleanroom Standards ISO Class (ISO 5, ISO 6, ISO 7, ISO 8)
Table of Contents
Common Terminology associated with Cleanroom
- Air Changes Per Hour (ACH) – The number of times the entire air volume in a room is replaced per hour to maintain cleanliness; ISO 7 rooms need ≥30 ACH.
- Ante Room – The entry room (ISO 7 or ISO 8) used for handwashing, garbing, and transition before entering the buffer room.
- Buffer Room – An ISO 7 room that houses the laminar flow hood or BSC, where sterile compounding takes place under controlled conditions.
- Certification – Professional testing (done every 6 months) to verify that ISO particle counts, airflow, and pressure requirements are being met.
- Critical Area – The space where sterile compounding occurs, including the direct compounding area (DCA) inside a laminar flow hood or BSC, requiring ISO 5 air.
- Environmental Monitoring – Ongoing testing of air, surfaces, and staff to ensure the cleanroom maintains ISO classification and regulatory compliance.
- HEPA Filter (High-Efficiency Particulate Air) – A filter that removes ≥99.97% of particles ≥0.3 microns; essential for maintaining ISO 5 air in laminar flow hoods and cleanrooms.
- ISO Class (ISO 14644-1) – International standard defining cleanroom air quality by setting maximum airborne particle limits per cubic meter (e.g., ISO 5, 7, 8).
- Laminar Airflow (Unidirectional Airflow) – Smooth, non-turbulent airflow that continuously moves filtered air over the work surface, sweeping away contaminants.
- Negative Pressure Room – A room where air pressure is lower than adjacent areas, containing hazardous vapors inside the room (used for hazardous drug compounding).
- Particle Count – Measurement of airborne particles (typically ≥0.5 microns) used to determine if the cleanroom or hood meets ISO class standards.
- Positive Pressure Room – A cleanroom where air pressure is higher than adjacent spaces, preventing outside contaminants from entering (used for non-hazardous compounding).
- ULPA Filter (Ultra-Low Penetration Air) – A higher-efficiency filter than HEPA, removing ≥99.9995% of particles ≥0.12 microns; used in specialized ultra-clean environments (not typical in pharmacy compounding).
Cleanroom Design and Features
What Are Cleanrooms?
Cleanrooms are specially designed, controlled environments where the amount of airborne particles, contaminants, temperature, humidity, and airflow are strictly regulated.In pharmacy, they are essential for ensuring sterile compounding conditions that meet USP <797> and USP <800> standards, helping prevent contamination of sterile medications.
Cleanroom Design
Cleanrooms are designed with specific airflow patterns and ventilation systems to control contamination.- ISO Class 5: Used for direct compounding of sterile preparations, typically in a laminar flow hood or compounding aseptic isolator (CAI).
- ISO Class 7: Surrounds the ISO Class 5 room and acts as a buffer to reduce contamination risk. This is the room where non-hazardous sterile compounding takes place before entering the ISO Class 5 area.
- ISO Class 8: The ante-room where personnel prepare and gown before entering the sterile compounding area. It serves as a transition space between the clean and less clean environments.
Features of Cleanrooms
- Equipped with HEPA filters to remove ≥99.97% of particles ≥0.3 microns.
- Maintains specific ISO air quality classes (like ISO 5, ISO 7, ISO 8) with defined particle limits.
- Designed with controlled air pressure (positive for non-hazardous; negative for hazardous drugs).
- Includes environmental controls for temperature, humidity, and airflow patterns.
- Uses smooth, easy-to-clean surfaces to minimize particle shedding.
ISO Definition & Class Levels
What is ISO?
ISO stands for International Organization for Standardization, a global, independent organization that develops international standards to ensure quality, safety, and efficiency across industries. In pharmacy and cleanroom contexts, we’re mainly referring to:ISO 14644-1 (Current Global Standard, Cleanroom Standards)
This ISO standard sets the air cleanliness classifications for cleanrooms and controlled environments, based on the maximum allowable number of particles (usually ≥0.5 microns) per cubic meter of air. It defines how “clean” a controlled environment is, which is critical for industries like:ISO Class Levels (From Cleanest to Dirtiest)
| ISO Class | Particle Size Measured (µm) | Max Particles/m³ (≥0.5 µm) | Common Uses |
| ISO 1 | ≥0.1, ≥0.2, ≥0.5 | ≤12 (≥0.5 µm) |
Nanotech, advanced semiconductor fabrication
|
| ISO 3 | ≥0.5 | ≤1,020 |
Critical pharmaceutical manufacturing, gene therapy
|
| ISO 5 | ≥0.5 | ≤3,520 |
Pharmacy IV compounding (USP <797>), laminar flow hoods, BSCs
|
| ISO 7 | ≥0.5 | ≤352,000 |
Buffer zones around ISO 5 areas, non-hazardous sterile prep
|
| ISO 8 | ≥0.5 | ≤3,520,000 |
Gowning rooms, medical device assembly, Storage
|
- Lower ISO number = cleaner environment (ISO 1 is the cleanest).
- ISO 5 is the standard for pharmacy laminar flow hoods and biological safety cabinets (BSCs).
- USP <797> requires:
- ISO 5 for direct compounding (e.g., inside a hood).
- ISO 7 for surrounding buffer areas.
- ISO 8 for anterooms, storage.
How ISO Class is Measured
Particle Counting
Laser particle counters measure airborne particles (≥0.5 µm).HEPA Filtration
ISO 5+ rooms require HEPA filters (99.97% efficiency at 0.3 µm).Air Changes Per Hour (ACH)
ISO 5 requires ≥90 ACH (critical for sterile compounding).Pressure Differentials
Cleanrooms maintain positive pressure to prevent contamination.Where Are Cleanrooms Used in Pharmacy?
- Buffer rooms (ISO 7): Houses laminar flow hoods or Biological Safety Cabinets (BSCs) for sterile compounding.
- Ante rooms (ISO 7 or 8): Used for garbing, handwashing, and preparation before entering the buffer room.
- Inside compounding devices (ISO 5): Direct compounding area (DCA) in laminar flow hoods or biological safety cabinets.
Certification Frequency for Pharmacy Cleanroom Equipments
| Equipment | Initial Certification | Certification Frequency |
| Laminar Flow Hood (LFH) | Before first use | Every 6 months |
| Biological Safety Cabinet (BSC) | Before first use | Every 6 months (or after moving) |
| HEPA Filters | At installation | Every 6 months (integrity) Replace when damaged |
| Compounding Isolators (CAIs, C-PECs) | Before first use | Every 6 months |
| Cleanroom (ISO 5/7/8) | At commissioning | Every 6 months (USP <797>) Annually (ISO 14644) |
Gowning and Personal Protective Equipment (PPE)
Proper gowning and PPE are required before entering cleanrooms, especially for ISO Class 7 and 5 environments, to prevent contamination from personnel.
- This includes wearing:
- Sterile gloves, gowns, hair covers, shoe covers, and face masks.
- Air Shower: Some cleanrooms, especially in ISO Class 8 areas, may include air showers to further reduce the introduction of contaminants.
- No jewelry, makeup, or perfumes
- Limited personnel movement to reduce turbulence
Donning PPE (Gowning) Sequence:
- Step 1: Wash hands thoroughly using soap and water, dry and apply hand sanitizer.
- Step 2: Put on a clean Gown. Ensure the gown covers your entire body, including your arms, and is securely fastened at the back or neck.
- Step 3: Put on Shoe Covers to prevent contaminants from shoes being carried into the cleanroom.
- Step 4: Wear a Hair Cover/Cap to cover all hair. This prevents hair from contaminating the cleanroom environment.
- Step 5: Put on a Face Mask or respirator to cover the mouth and nose, ensuring that it fits snugly.
- Step 6: Place the Face Shield/ Goggles (if required) for additional protection.
- Step 7: Put on sterile or non-sterile gloves. Ensure the gloves fit tightly around the wrists and overlap with the gown sleeves.
De-gowning PPE Sequence:
- Step 1: Carefully remove the gown by unfastening it and rolling it inside out as it is removed. Avoid touching the outside of the gown.
- Step 2: Remove the face shield or goggles by handling only the straps or side frames, not the front of the shield.
- Step 3: Remove Face Mask – Remove any mask or respirator.
- Step 4: Remove Hair Cover/Cap – by handling only the edges, being careful not to touch the outside of the cap.
- Step 5: Remove Shoe Covers carefully by pulling them off without touching the outside of the cover. Dispose of shoe covers in the appropriate waste container.
- Step 6: Remove Gloves: Remove gloves carefully to avoid touching the outside of the gloves. Grasp the cuff and pull the gloves off inside out. Dispose of gloves in a designated waste container.
- Step 7: Hand Washing: Wash your hands thoroughly using soap and water after degowning to ensure that any remaining contaminants are removed.
Storage of Raw Materials, Finished Products, Hazardous and Non hazardous Compounds
| Storage Type | ISO Class | Storage Requirements |
| Raw Materials (Non-Hazardous) | ISO Class 8 | Stored in ante-room or buffer zones, temperature-controlled. |
| Finished Products (Non-Hazardous) | ISO Class 7/8 | Stored in ISO Class 7 buffer zone or ISO Class 8 ante-room with required temperature control. |
| Refrigerators (Non-Hazardous) | ISO Class 7/8 | Stored in ISO Class 7/8 cleanrooms, refrigerated storage for temperature-sensitive products. |
| Raw Materials (Hazardous) | ISO Class 7/5 | Stored in ISO Class 7 or 5 cleanrooms with specialized containment. |
| Finished Products (Hazardous) | ISO Class 7/5 | Stored in designated hazardous drug areas (ISO Class 7/5), often in lockable cabinets. |
| Refrigerators (Hazardous) | ISO Class 7/5 | Stored in dedicated, lockable refrigerators/freezers in ISO Class 7/5 environments. |
Security and Access Control in Cleanrooms
- Restricted Access Areas: Cleanrooms, especially those classified under ISO 7 and ISO 5, require strict access control to prevent contamination and maintain the sterility of the environment. Only authorized and trained personnel are allowed to enter, with access often limited to those involved in compounding or handling critical materials.
- Gowning and Personal Protective Equipment (PPE): Personnel entering cleanrooms must enter with appropriate PPE, including lab coats, gloves, hairnets, face masks, and shoe covers. These garments prevent contaminants from being transferred into the cleanroom. In some cases, air showers or gowning rooms may be used before entry into more sterile areas like ISO Class 5.
- Electronic Access Systems: Cleanrooms may employ keycard access or biometric systems to track personnel entering or exiting. This ensures only trained individuals can access sensitive areas and provides accountability in case of contamination or breach.
Waste Disposal in Cleanrooms
- Waste Segregation: In cleanrooms, materials must be disposed of in designated waste bins to prevent contamination. Hazardous and non-hazardous wastes must be clearly separated, with hazardous materials placed in leak-proof, puncture-resistant containers.
- Controlled Disposal: Waste, especially hazardous or sterile materials, should be transported through non-cleanroom pathways to avoid contamination. Containers should be sealed, labeled, and documented. Refrigerators and freezers housing sensitive compounds also require careful handling during disposal.
- Monitoring and Records: Waste disposal should be tracked with detailed records of the type, quantity, and disposal method, ensuring compliance with regulatory standards and maintaining a clean, safe environment.
Aseptic Techniques
Pharmacists working in ISO Class cleanrooms must adhere to aseptic techniques. This includes:- Sterile handling of ingredients and equipment.
- Regular cleaning and disinfection of surfaces.
- Maintaining strict contamination control throughout the compounding process.
Cleaning and Maintenance of Cleanrooms
- Regular cleaning is crucial for maintaining a controlled environment. Surfaces must be sanitized using cleaning agents that do not introduce contaminants.
- Environmental monitoring must be performed to ensure the room’s cleanliness, including air sampling and surface testing.
- Equipment used for compounding must also be maintained and regularly disinfected to avoid cross-contamination.
Room Monitoring and Documentation
- Cleanrooms need constant monitoring to ensure that environmental conditions remain within acceptable limits.
- Temperature, humidity, and airflow need to be recorded periodically.
- Documentation should include maintenance logs, environmental monitoring results, and calibration records for equipment.
Handling Hazardous Drugs
- Special considerations must be given to hazardous drugs, which are compounded in more controlled environments like ISO Class 7 or Class 5 areas, using equipment such as biological safety cabinets (BSC) or compounding aseptic containment isolators (CACI).
- These areas must be equipped to safely contain hazardous drug particles, ensuring they do not escape into the environment.
