Sterile Manufacturing Cleanroom
The production of sterile preparations should be carried out in clean areas, entry to which should be through airlocks for personnel and for goods. Clean areas should be maintained to an appropriate standard of cleanliness and supplied with air that has passed through filters of an appropriate efficiency. The various operations of component preparation (such as containers and closures), product preparation, filling and sterilization should be carried out in separate a clean area. Clean areas for the production of sterile products are classified according to the required characteristics of the air, in grades A, B, C and D.
To obtain air of the required characteristics, methods specified by the national authorities should be used. It should be noted that: Laminar airflow systems should provide a homogeneous air speed of about 0.30 m/s for vertical flow and about 0.45 m/s for horizontal flow but precise air speeds will depend on the type of equipment. In order to reach the B, C and D air grades, the number of air changes should generally be higher than 20 per hour in a room with a good airflow pattern and appropriate HEPA (high-efficiency particulate air) filters. Low values for contaminants are reliable only when a large number of air samples are taken.
Preparation of components and most products should be done in at least a grade D environment in order to give low risk of microbial and particulate contamination, suitable for filtration and sterilisation. Where there is unusual risk to the product because of microbial contamination, for example, because the product actively supports microbial growth or must be held for a long period before sterilisation or is necessarily processed not mainly in closed vessels, preparation should be done in a grade C environment.