Cleanroom standards for Medical Device Production
Comprehensive Guide for Regulators and Manufacturers
Introduction
Cleanrooms are vital for producing sterile medical devices, impacting product quality. This guide assists regulators in understanding and inspecting cleanroom processes, based on current regulations, and provides management references for manufacturers. It emphasizes compliance during inspections.
The main function of A Clean Room is to control the cleanliness, temperature and humidity of the atmosphere to which the product is exposed, so that the product can be produced, manufactured and tested for microorganisms in a good environment.
Inspection Points and Procedures
1. On-site observation of the company's production and inspection of the clean room (area) environment
- Whether the flow of people and logistics in the clean room (area) intersects
- Whether shoes are changed, outer clothes are taken off, and hands are washed when entering
- Whether clean work clothes (shoes) or sterile work clothes are worn when entering
- Whether the second shift is equipped with a dressing mirror and facilities
- Is there a buffer room or air shower?
Key Considerations:
- Staff hygiene and clothing procedures
- Room cleanliness and maintenance
- Equipment and facility requirements
- Material handling protocols
The inspection continues with detailed checks on:
- Do the staff in the clean room wear slippers, put on makeup, wear accessories, etc.?
- Are there any auxiliary function rooms such as sanitary ware rooms, laundry rooms?
- Whether the necessary water pipes and pools are set up in the sanitary ware room
- Whether special functional rooms corresponding to the product production process are set up
- Whether a material entrance is set up with proper purification treatment
CleanRoom Classification
Cleanliness level | Maximum allowable number of dust particles (pieces/m³) | Maximum number of microorganisms allowed |
---|---|---|
100 level | 3,500 (≥0.5μm), 0 (≥5μm) | 5 (Planktonic), 1 (Settling) |
10,000 level | 350,000 (≥0.5μm), 2,000 (≥5μm) | 100 (Planktonic), 3 (Settling) |
100,000 level | 3,500,000 (≥0.5μm), 20,000 (≥5μm) | 500 (Planktonic), 10 (Settling) |
300,000 level | 10,500,000 (≥0.5μm), 60,000 (≥5μm) | 15 (Settling) |
Setting Principles
The "Medical Device Production Quality Management Standards" (Trial) from 2009 outlines clean room requirements for implantable and sterile medical devices. Manufacturers must determine and verify their clean environment levels based on these standards and regulatory guidelines.
To minimize contamination, manufacturers should employ advanced production technologies and processes. Reducing human interaction with products is essential, aiming to limit exposure to the operating environment and avoid direct contact whenever possible.
Cleanroom Management Requirements
General Requirements
Sterile medical devices and diagnostic reagents should be produced in environments with fresh air, low dust, and minimal bacteria. Avoid locations with wind, sand, or industrial pollution, and select sites upwind from pollution sources. Clean rooms need to be distanced from railways and highways.
Key Features:
- Air damping filter layer installed at the return air outlet
- Residual pressure valve for high sensitivity control
- differential pressure electric Air volume regulator
- Openable single-layer louver return air outlet
Environmental Control Requirements
The air purification process involves several key aspects:
- Filtration: Filters control the cleanliness of air entering the room, effectively removing bacteria that attach to particles.
- Airflow Management: Proper airflow helps eliminate existing pollutants, diluting particles and bacteria with Clean air.
- Air Pressure Control: Maintaining a static air pressure greater than 5 Pa prevents external pollution and cross-contamination.
Control Principles:
- Ensure air entering the clean room is fully sterilized
- Rapidly absorb and expel indoor microbial particles
- Prevent the accumulation and reproduction of these particles
- Limit the spread of bacteria from people or objects
Disinfection Control Requirements
The clean rooms (areas) used for medical device production are different from other industrial clean rooms (areas). The disinfection methods should be determined according to the process flow of different products and the risk control requirements.
1. Ultraviolet light sterilization
Ultraviolet sterilization lamps are widely used by manufacturers. They are mainly used for disinfection of clean workbenches, laminar flow hoods, material transfer windows, air showers and even the entire clean room.
2. Ozone disinfection
Ozone, found in nature, disinfects by decomposing into oxygen and reactive oxygen atoms, which effectively kill bacteria by damaging their cell membranes.
3. Gas sterilization
Traditional air sterilization involves using disinfectants like formaldehyde to produce gas fumigation. Formaldehyde is most effective at 65% humidity and 24-40°C.
4. Disinfectant fire bacteria
The walls, ceilings, doors, windows, machinery and equipment, instruments, operating tables, carts, tables, chairs and other surfaces should be cleaned regularly.
This guide outlines common questions to consider during inspections and provides references to authoritative sources for further reading.
Common Inspection Questions
1. Environmental Conditions
Inspect that all HVAC systems are functioning properly to maintain the specified conditions (temperature, humidity) within regulatory limits.
2. Airflow Verification
Verify the effectiveness of air filtration and direction, ensuring compliance with ISO cleanliness standards to prevent contamination.
3. Filter Maintenance
Confirm that hepa or ULPA filters undergo periodic testing and replacement as per schedule.
4. Documentation
Ensure all logs, including cleaning schedules and maintenance records, are accurate and current.
5. Personnel Procedures
Observe compliance with gowning and de-gowning procedural protocols to prevent contamination.
6. Materials Compliance
Check that all surfaces, walls, and flooring within the cleanroom meet required standards for materials and finishes.
7. Emergency Protocols
Confirm that emergency procedures and escape routes are visible and unobstructed.
8. Equipment Calibration
Ensure that all instruments and equipment are regularly calibrated to maintain accuracy.
References
- ISO 14644-1:2015 - Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness by particle concentration.
- FDA Guidance for Industry - Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice.
- GMP Annex 1 - Manufacture of Sterile Medicinal Products (EudraLex, Volume 4).
- ISO 13485:2016 - Medical devices - Quality management systems - Requirements for regulatory purposes.
- IES Guidelines - Institute of Environmental Sciences and Technology, various publications on contamination control.
- USP <797> Guidelines - Compounding Sterile Preparations Standards.
- ASHRAE Standards - American Society of Heating, Refrigerating and Air-Conditioning Engineers, specific standards related to cleanroom environments.
- CDC Guidelines on Environmental Infection Control - Recommendations relevant to maintaining sterility and hygiene in healthcare settings.
This guide serves as a helpful tool in conducting thorough inspections of cleanroom environments for medical devices, ensuring these controlled areas meet all necessary regulatory and compliance standards.