- ISO 14644-1: Specifies the maximum allowable concentration of particles in the air and outlines testing and monitoring procedures to ensure air cleanliness in cleanrooms and controlled environments.
- CFR Title 21 Part 211: Outlines the current good manufacturing practice (cGMP) requirements for cell and gene therapies. It covers all aspects of manufacturing, including facility design, equipment validation, and documentation.
- FDA Guidance for Industry - cGMP for Phase 1 Investigational Drugs: This guidance document provides recommendations for the manufacture of investigational drugs for use in Phase 1 clinical trials. It covers topics such as facility design, environmental monitoring, and personnel qualifications.
- EMA Guidelines on GMP Specific to Advanced Therapy Medicinal Products: Requirements for the manufacturing of advanced therapy medicinal products, including cell and gene therapies.
- WHO Guidelines on GMP for Biological Products: Recommendations for the manufacture of biological products, including cell and gene therapies. They cover all aspects of manufacturing, including facility design, equipment validation, and documentation.
It is important to note that these standards and regulations are not exhaustive, and additional guidelines may apply depending on the specific product being manufactured and the regulatory jurisdiction in which it is being produced.
Cell and Gene Therapy cleanrooms can be certified by a third party in many ways. Some common options include:
- Particle counting: Measures airborne particle concentration using particle counters.
- Airflow velocity measurement: Measures airflow velocity using an anemometer or similar device.
- Filter Integrity Testing: Ensure there are no pin holes that are compromise the performance of the HEPA filter.
- Smoke studies: Introduces smoke to observe airflow movement and design.
- Pressure differential measurement: Measures pressure differential to ensure proper isolation from outside contamination.
- Microbial sampling: Tests for presence of microorganisms or CFU (Colony Forming Units) to ensure cleanroom is free from viable contamination.
To maintain the standard of this certification, a cleanroom should be checked – at 6 month intervals for ISO 5 and 12 month intervals for ISO 6 and above – using the same or similar methods to the certification process.
- Use of appropriate personal protective equipment (PPE)
- Proper gowning and degowning procedures
- Establishment and maintenance of a cleanroom environment that adheres to standards and regulations
- Implementation of proper cleaning and disinfection procedures
- Adherence to aseptic technique
- Proper handling and storage of materials and equipment
- Proper cleanroom balancing to maintain positive cascading pressure (from the main cleanroom to the anterooms then to the outside)
- Regular monitoring and testing of the cleanroom environment to ensure continued compliance and minimize the risk of contamination.
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ICS is a top-tier cleanroom supplier that specializes in creating intentional and customized designs to meet clients' specific needs within industry-leading timeframes. All our cleanrooms are fully certified by third-party organizations, ensuring the highest standards of cleanliness and quality. With six decades of experience in cleanroom construction, we have won notable awards, including the Department of Energy's Small Business of the Year.
Frequently asked questions
Cell and Gene Therapy typically require a higher level of sterility than most other manufacturing practices. In general, a cleanroom for CGT applications will need to have:
- High-efficiency particulate air (HEPA) filters to remove particles from the air down to at least ISO 7.
- A Class II Type A2 BSC providing ISO 5 quality air.
- CO2 and N2 gaseous supply.
- A material passthrough and a anteroom.
- Adequate power for refrigerators and incubators.
- Positive cascading pressure to minimize the introduction of particles and contaminants.
- Proper gowning procedures for personnel entering the cleanroom.
- Environmental monitoring and testing of the cleanliness level to ensure compliance with industry standards.
If you are looking for a rapid solution to the cleanroom space for your new cell or gene therapy candidate, our mobile cleanroom can be delivered in around a week. For more specific questions regarding your cleanroom and specification, please contact us.
- Cleanliness requirements: The level of cleanliness required for the specific cell and gene therapy application must be determined before purchase, as this will impact the design of the cleanroom.
- Size and layout: The size and layout of the cleanroom must be designed to meet the specific manufacturing process requirements while maximizing the use of available space. Cleanroom size (cubic volume) will also impact the HVAC requirements, which will have an effect on the efficiency of the cleanroom.
- Air filtration and ventilation: Proper air filtration and ventilation are critical in cleanroom design to ensure that the cleanroom meets the necessary cleanliness requirements. Ensuring the cleanroom has enough capacity to ”breathe” is critical to allow for a proper air change rate.
- Gowning and personnel flow: Proper gowning procedures and personnel flow must be established to minimize the introduction of particles and contaminants into the cleanroom.
- Equipment and materials: Assessing the equipment and materials used in the manufacturing process is critical to helping maintain the clean environment. One example is pneumatically operated equipment within the cleanroom. If general, unfiltered air or lightly filtered air is being used to operate a tool within the cleanroom, the exhaust may cause a great amount of contamination. To avoid this it would be best to add a point of use millipore filter or use a clean and dry inert gas like nitrogen.
- Monitoring and control: The cleanroom must have a monitoring and control system in place to ensure that the necessary cleanliness requirements are maintained. Without an environmental monitoring system, the cleanroom environment might give no degradation or failure warning before your next certification.
- Biosafety cabinets: These cabinets provide a sterile work environment and are equipped to prevent the spread of contaminants.
- Incubators: Incubators are used to maintain a controlled temperature and humidity for cell culture. These can be CO2 incubators for mammalian cell cultures or anaerobic incubators for microbial cultures.
- Centrifuges: Centrifuges are used for separation and purification of cell and gene therapy products. They can be refrigerated for temperature-sensitive samples and can operate at high speeds for efficient separation.
- Microscopes: Microscopes are used for the evaluation of cell cultures, cell viability, and transfection efficiency.
- Liquid nitrogen storage: Liquid nitrogen storage tanks are used for the long-term storage of cell lines, primary cells, and gene therapy products. These tanks maintain a temperature of -196°C to preserve the biological samples.
- Autoclaves: Autoclaves are used for sterilization of equipment and materials used in the cell and gene therapy manufacturing process.
- pH meters and other analytical instruments: Used to monitor the quality and characteristics of cell and gene therapy products during the manufacturing process.
- Cleaning equipment: Cleaning equipment such as vacuum cleaners, mops, and wipes are used for the regular cleaning and maintenance of the cleanroom environment.
The specific equipment used in a cell and gene therapy cleanroom will depend on the manufacturing process and the requirements of the therapy being produced. It is important to ensure that all equipment used in the cleanroom is properly validated and maintained to ensure that it is functioning correctly and does not introduce contaminants into the environment.