Cleanrooms require clean air. But how can air cleanliness be defined? We normally differentiate between particulate and microbiological contamination of air. Contamination must remain below certain levels which are specified in the GMP regulations. This chapter deals with the monitoring of the particulate cleanliness of air, also referred to as particle monitoring.
Compliance with the specified cleanliness grade must be tested at regular intervals or on a continual basis. Monitoring has established itself as the preferred method for determining airborne particles. Particle counters are used that suck in an air sample, count the particles in the sample and classify them by size. However, they do not differentiate between viable microorganisms and other particles in the air. As opposed to air samplers, particle counters deliver the result immediately after completion of the measuring interval.
There are two different particle monitoring processes:
GMP-compliant continuous monitoring systems have been used for more than 20 years. The systems were initially developed for existing Windows platforms and the data were stored, e.g. as Excel files. The requirements have become stricter on account of the increasing demand for data protection and manipulation protection of raw data, and because monitoring data is considered to be production-related information. The software of computerised monitoring systems must comply with the requirements for computer validation (e.g. GAMP®5). A large number of automated monitoring systems for recording and documenting production-related data are now available. Particle monitoring systems have a large market share. To ensure that these systems can be used in pharmaceutical companies, the applicable requirements had to be met. Thestandard functions include an audit trail, different password levels for access rights and encryption of raw data (i.e. tamper protection).
Optical particle counters count and classify particles based on their scattered light intensity (standardised scattered light diameter). The individual particles are guided through a laser beam. The scattered light impulse generated by the particle is photoelectrically detected.
Figure 1: Schematic representation of an optical particle counter with 90° light-scattering detection (source: VDI 3489, Part 3)
1. Inlet tubing
2. Aerosol nozzle
3. Inlet for clean air jacket
4. Illuminating beam
6. Measuring volume
7. Light trap
8. Measuring cell housing
9. Suction funnel
10. Dimming lens
How does a particle counter function?
The particles pass through the laser beam in the measuring cell. The beam is ideally several times thicker than the particle. This ensures that the particle passes through a practically homogeneous light field. The theoretical analysis is based on perfectly round particles, e.g. latex spheres that are generally used for the calibration of particle counters. The particle counter always detects the intensity of the scattered light emanating from the particle being measured.
As soon as the particles start to pass through the laser beam in the measuring cell, scattered light is created that is measured by the scattered light detection system, and the data is transferred to a downstream electronic system. An analogue signal is created from the light data. If a particle passes through the measuring cell, short-term scattered light intensities are created and, as a result, electrical pulses. These are counted by the optical particle counter and classified using a pulse height detection system. This facilitates the detection of different scattered light intensities and thus different particle sizes. After the pulse height analysis, the counts are digitally assigned to the individual size classes and displayed at the end of the measuring interval. Figure 2 contains a summary of this functional principle.
Figure 2: Functional principle of a particle counter
|Functional principle of a particle counter|
The lower particle size limit of detection depends on the type of device. The upper limit is determined by sample-taking and electronic overload rather than by the method used for measuring.
The count rate is used to determine the particle concentration, and the amplitude of the pulse is used to determine the particle size. To determine the particle concentration, the volume flow rate through the measuring field must also be known.
Apart from the particle diameter, there are other factors that have an impact on the intensity of the scattered light created by the particle:
Figure 3: Schematic representation of a "real" particle when hit by a laser beam and the relevant photo-optical parameters that have an impact on the creation of scattered light
(source: MT-Messtechnik, Adelzhausen)
Scattered light measurement using real particles is a double indirect measurement. For this reason, larger measurement errors must be expected during the actual measurement depending on the material and the properties of the particles.
Double indirect measurement means:
To ensure compliance with the limit values for the air cleanliness grades, the particle size concentrations measured during monitoring should be clearly below the limit value.
A major advantage of particle measurement is the immediate availability of the result after each measuring interval. On the other hand, the fact that this method does not differentiate between viable and non-viable particles is a disadvantage. For this reason, the operator has to carry out additional air sampling.
The text is an excerpt of the GMP MANUAL, Chapter 3.K Particle Monitoring
Thomas von Kahlden
CCI - von Kahlden GmbH, Leinfelden-Echterdingen, Germany