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Particle Sciences - Technical Brief: 2010: Volume 9
Cleanrooms are defined as a room or suite of rooms, in which the concentration of airborne particles is maintained within established parameters and where other factors are controlled to within specified limits. These rooms are designed to provide control of environmental factors including:
Applications include the manufacture of sterile and non-sterile pharmaceutical and biotech products, medical devices, and implants. These rooms are also used to manufacture sensitive electronics. However, the requirements for these latter applications are not the objective of this article. GMP requirements from the different Boards of Health, including the US Food and Drug Administration (FDA), for sterile pharmaceutical, biotech, medical devices and implants require the manufacture of these products are performed in clean environments that meet the requirements of standards such as ISO EN146441.
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Room air should be supplied by an external air conditioning system, preferably dedicated to the facility. Partial recirculation of room air is appropriate and this allows for optimal energy utilization. Sufficient fresh air should be supplied in accordance with ventilation codes, to balance exhaust air and to maintain specified pressures. Unless, otherwise specified, typical temperature range for this kind of room is within the range of 16 to 19 °C and relative humidity of approximately 50% is maintained. The type of equipment and number of people in the room may dictate where in the range you need to be to assure that during production the operations area is maintained at the right temperature and humidity levels.
Only HEPA filtered air should enter the cleanroom and the gowning areas. These modules are available in fan assisted with fan speed control and should operate at a velocity of 90 ± 10 fpm or 0.45 ± 0.05 m/s. The location of the HEPA filters and air return grilles should create air movement from the designated ‘clean zone’ to the ‘less clean’ zones. Return air grilles should be at a lower level to aid in laminar flow requirements.
Air supply to the cleanroom should provide a room air change rate of >20 per hour. Air cleanliness will be enhanced by higher air change rates. When the doors are opened the supply air volume should maintain an outward flow of air.
In order to control contamination, operators and those in charge of a cleanroom need to be cognizant of sources of contamination. These include:
People are a major source of contamination in the cleanroom (Table 1). Notice the number of particles produced per minute during these activities.
Cleanroom Classifications as specified by different standards are shown in Table 2. Non-sterile products are typically produced in an ISO 8 or EU Class D environment. Sterile products are required to be filled and stoppered in an ISO 5 or EU Class A environment.
As an example, here are some recommended procedures for cleaning a Class C or ISO 7 Area cleanroom. These procedures are simply guidelines, not standards or rules. It is important to review all cleaning procedures to be used in a cleanroom with responsible management. A detailed cleaning schedule should be prepared for every cleanroom.
Procedure – Good housekeeping and maintenance of the cleanroom and the associated restricted areas are essential to assure quality. Cleaning of an active cleanroom should be performed daily. However, if the room is not used daily, a different schedule may be implemented, but it should be cleaned after every use. Improper cleaning of the cleanroom can lead to contamination and compromise product quality. Proper selection of equipment, cleaning agents and cleaning materials is important for proper cleaning. Only products that have proven cleanroom performance records should be considered for use. These products should be listed in appropriate policies or procedures and all vendors should be informed about the strict policies of how products are qualified. All procedures should be strictly enforced. Below are some examples of how to organize cleanroom cleaning. These are guidelines for preparing work procedures and schedules. Local requirements must be included in any cleaning program.
Equipment and supplies – all supplies must meet the Class C or ISO 7 Area minimum requirements
Cleaning Tasks – frequency may vary depending upon local requirements
General Cleanroom Requirements – Here is a list of general requirements recommended as a minimum for the successful operation of a cleanroom. All cleanroom personnel should be aware and follow these requirements at all times.
HEPA Filter - High Efficiency Particulate Air Filter
Viable - a particle capable of living, developing, or germinating under favorable conditions, i.e., bacteria.
Non-viable - typically dust or liquid particles
Airborne - carried by or through the air
For handling potent compounds, i.e., toxic materials, in addition to the requirements described for a cleanroom, precautions need to be taken to avoid spreading the toxic material to adjacent areas. This may be achieved by maintaining a negative pressure differential between the cleanroom and adjacent area so any hazardous powder or aerosol is contained within the cleanroom, i.e., P3 ~ P2 > P1 (Figure 1). This is accomplished by designing the facility with HEPA filtered incoming air and providing HEPA filtration at the exhaust. Also providing a higher flow through the exhaust filters to assure proper flow, pressure differential and sufficient air changes in order to meet the required room classification; this setup does not allow air from the cleanroom to enter into adjacent areas. Additionally, by providing localized exhaust or incorporating isolators onto manufacturing equipment, the control of aerosols and dust from handling powders is increased. Note that personnel enter the cleanroom through the gowning area whereas equipment and materials are brought through the air lock.
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