FDA Clean Room Requirements
Clean rooms are enclosed spaces where manufacturers apply environmental controls to prevent contamination of the products, focusing primarily on limiting the concentration of particulates in the air. The U.S. Food and Drug Administration publishes clean room standards, both required and recommended, for manufacturers of pharmaceuticals and medical devices. Contaminants are continually introduced into an environment by people, equipment, processes and facilities. Clean air standards are applied continuously to remove contaminants and prevent the introduction of contaminants into the environment.
The FDA requirements for clean rooms are taken from current good manufacturing practice, or CGMP, regulations. The CGMP regulations involving manufacturers of sterile biological products and drugs are in the Code of Federal Regulations at 21 CFR 210 and 211, Current Good Manufacturing Practice for Finished Pharmaceuticals. The CGMP regulations at 21 CFR 600 through 680 provide additional requirements for biological products. The FDA requires that in questions of compliance, any regulations that apply specifically to the drug product in question supersede the generally applied CFR 210 and 211 regulations.
The FDA clean room regulations require strict environmental controls, beginning with planning and construction of the rooms, to achieve clean air standards in clean rooms. Regulations require a monitoring system for environmental conditions in the clean room, which must be a separate, adequately-sized room that has equipment to control humidity, dust, air pressure, temperature and microorganisms. Regulations also require an air filtration system, as well as written procedures for preventing contamination, and for cleaning and sanitizing all surfaces and equipment.
Clean air standards rate a clean room’s air cleanliness based on the levels of airborne particulates. The monitoring system required by the FDA includes testing for airborne particulates and keeping the results within optimal levels. While Federal Standard 209E was the standard most often used in the United States since the 1960s, the General Services Administration announced the cancellation of 209E in 2001, and recommended the use of International Standard ISO 14644, Classification of Air Cleanliness. The eight-part ISO 14644 includes instructions for classification of air cleanliness, tests and monitoring, design and construction, operation, and classification of airborne molecular contamination.
The FDA provides guidance based on clean room regulations. Because every action results in airborne particulates -- a motionless person adds 100,000 particles size .03 microns or larger per minute to a room -- clean room requirements prohibit certain items and activities, including jewelry and fast motions. Depending on the ISO class, workers wear special clothing and suit up in a gowning room before entering the clean room through an interlocking door.