Air Cleanliness Test (Nonviable Particle Counting)
The concentration of nonviable particles is used as a quick estimate of the overall cleanliness of the environment because of the versatility and fast response offered by the airborne particle counters. Although there is no proved correlation between viable and nonviable particle concentration, the assumption is frequently made that the level of nonviable particles provides a good indication of the overall environmental airborne bioburden.
Airborne concentrations are measured with white light, laser, or condensation nuclei particle counters. Hardware and provided system software vary, depending on the manufacturer, although all of these systems are standardized following the IES and ASTM standards. As indicated, air cleanliness classification for controlled environments has occasionally been based on the concentration of particles of a specific size per unit of volume. The standard currently in use for this characterization is the ISO 14644-1 Cleanrooms and associated controlled environments-Part 1: classification of air cleanliness published by the ISO. Although a nonmandatory standard for pharmaceutical industry, the sampling methods expressed in this standard, as well as the statistical manipulation of the data obtained can be applicable and approvable for the FDA, EMEA and other regulatory agencies around the world.
The acceptance criteria, sampling location, and sample size should be carefully set. The number of samples suggested by the ISO Standard and sample volumes may not reflect the criteria used for a system that is primarily dedicated to avoid microbial contamination. The expectations are that the conditions prevailing during the media fills constitute the real operational standard for the critical environment. Therefore, more than two sampled points are suggested during qualification, preferably in those areas where the containers, stoppers, or closures remain exposed to the environment for a longer time. The principles and methodology suggested in the HACCP and depicted in ISO standard provide a better guidance for the number and location of sampling points.
The statistical handling of the data suggested by the ISO Standard is acceptable for the FDA, as long as no counts exceeding the class level are averaged. When a single count exceeds the set limit for the environment, the FDA considers it a failure.
The use of grids for sample site selection is often employed as an alternative method that provides a systematic approach. Locations can be easily identified and used for other tests, such as the airborne bioburden and surface bioburden assessments. The typical size of the squares varies from 2 X 2 ft in the critical environments to 5 X 5 ft in the controlled environments. This approach provides extensive support for statistical determinations. The induction leak test using smoke generation and particle counters with personnel present permit a better identification of potentially critical locations as a function of personnel practices and equipment operation.
Test objective: To determine that the complete as-built, operational facility meets the air cleanliness requirements specified in the process functional requirements.
- Critical environments: The particle concentration under dynamic conditions should not be more than 3.5 particles of 0.5 nm and larger per cubic meter (100 particles of 0.5 nm and larger per cubic foot).
- Other environments: Typically a tenfold gradient is used from critical to less critical environments (i.e., 1000 for environments adjacent to critical environments, 10,000 for those adjacent to it, and so on).
- Test procedure
- In general, the environment is divided by a grid, depending on the configuration of the room and classification of the environment. A 60 X 60cm (2X 2ft) grid is typically used for critical environments.
- Larger squares (twofold projection) are used for less critical environments in ascending order. Sampling locations typically are at work height and as close to the operators as possible.
- Frequently, a chart recorder attached to the particle counter is used to facilitate data collection and documentation procedures.
- Reporting requirements
- Report results in the approved forms.
- Specify the basis for the acceptance or rejection as a function of the acceptance criteria.
reference by: validation of pharmaceutical process by james and fredrick