Hach Whitepaper ISO 21501 - 4 Calibration of Air Particle Counters from a Metrology Perspective

The ISO 21501-4 calibration standard for Light Scattering Air Particle counters (LSAPC) is being increasingly adopted by pharmaceutical manufacturing companies. Calibration of APC instruments is a broad and complex subject of interest to a wide variety of stakeholders. For example production engineers, cleanroom validation technicians, micro-biologists and QA specialists. The informational needs of each of these groups vary considerably. Some will require to understand the ‘regulatory and compliance’ impact of the new standard whereas others have a more technical interest in the calibration itself. This paper is intended to serve the latter, essentially in a metrologists perspective. Introduction ISO 21501-4 is a relatively new calibration standard covering the performance and periodic calibration of lightscattering air particle counters (LSAPC or APC) throughout the instruments life. This international standard, which builds upon earlier regional standards and recommended practices characterized by a broader range of tests, deals comprehensively with statistical uncertainty and defines limits to a set of performance parameters which must be covered in routine periodic calibration. Conformance to ISO 21501-4 has ensured that APC instruments both size particles correctly to an acceptable uncertainty level as well as count particles accurately to a defined counting efficiency level. Calibrating instruments to the new standard requires more sophisticated calibration systems in terms of equipment, methods and algorithms. This paper discusses the various elements of the standard, methods and required limits. A discussion on the combined uncertainty for the calibration is included in the appendix. Historical Calibration Method and Standards ISO 14644 is a cleanroom management standard, widely used for cleanroom classification and environmental monitoring. Despite the existence of ISO 14644, prior to 2007 there was no ISO standard addressing the calibration and performance of the particle counters (APC) used to classify cleanrooms to ISO 14644. However, non-ISO standards and calibration methods guidelines did exist prior to ISO 21501-4 and were employed by most major manufacturers of optical particle counting instruments. The standards typically referred to at that time included: ASTM F 328-98(2003) “Standard Practice for Calibration of an Airborne Particle Counter Using Monodisperse Spherical Particles” (withdrawn May 2007). IEST-RP-CC014.1 “Calibration and Characterization of Optical Airborne Particle Counters” . JIS B 9921:1997 Japanese standard which comprehensively deals with APC design and performance, which is still widely regarded today. While these standards were quite comprehensive in scope, they did not deal adequately with routine calibration and performance metrics throughout the life of the instrument. For example counting efficiency, a critical parameter, was not required to be re-assessed during periodic recalibration, particularly on-site calibrations.