Particle Monitoring Requirements in Pharma Cleanrooms

Understanding Particle Monitoring Requirements in Pharma Cleanrooms starts with knowing the current requirements of existing regulations. EU GMP Annex 1 and The International Standard, ISO 14644-1 are the current international standard of defining cleanroom contamination levels. The cleanroom standards however are applicable to all types of cleanroom, whether they are for industrial applications, highly sensitive semiconductor manufacture, or for sterile (aseptic) production.

Pharmaceutical cleanrooms are classified according to the particle concentration of the air that is required to meet the cleanliness criteria for the manufacturing process being performed. Using the ISO 14644-1 standards, the lower the classification number, the lower the particle concentration. Originally cleanrooms were classified according to the number of particles per cubic foot at 0.5 microns (µm) as this was the most reliable size that could repeatedly be tested. The determination of the cleanroom class is a process based on actual statistically valid measurements, segregated into three phases:

As-Built: a completed room with all services connected and functional, but without production equipment or personnel within the facility.
At Rest: all the services are connected, all the equipment is installed and operating to an agreed manner, but no personnel are present.
Operational: all equipment is installed and is functioning to an agreed format, and a specified number of personnel are present, working to an agreed procedure.

The airborne particle count test is performed by counting particles at defined grid locations within the cleanroom. The number of measurements taken at each test point depends on the cleanroom class and the statistical requirements specified in the standards. The standards also state that the data should permit defining the classification level with 95% confidence level. It is recommended that a particle counter capable of 0.5 µm sensitivity be used for the definition of the ISO classes used pharmaceutical manufacturing. Pharmaceutical cleanrooms typically operate at Class 5 (most aseptic areas), Class 7 (surrounding areas), or Class 8 (support areas). The minimum number of samples required for a specific area is explained in the paper, ISO 14644-1:2015 Revisions Summary.

Once we have proven that a cleanroom meets a cleanroom classification standard using a particle counter, the classification achieved dictates which production activities can be performed in that cleanroom. Download the full paper to learn more about the following: