The application of the ventilation equations to cleanrooms - Part 2: Decay of contamination

This article is the second of a three-part series that investigates the application of the ventilation equations to designing and testing cleanrooms. This part is concerned with the decay equation. The recovery test, described in ISO 14644-3 (2005) is discussed, and improvements recommended. The application of the decay equation to the ‘clean up’ requirement given in the EU GGMP (2008) is also discussed. Finally, a method is considered that calculates the time needed for airborne contamination in cleanroom areas to decay to acceptable concentrations

A cleanroom contamination control system

Analytical methods for hazard and risk analysis are being considered for controlling contamination in pharmaceutical cleanrooms. The most suitable method appears to be the HACCP system that has been developed for the food industry, but this requires some reinterpretation for use in pharmaceutical manufacturing. This paper suggests a possible system. To control contamination effectively, it is necessary to have a good appreciation of the routes and sources of contamination, and the means of controlling them. An overview of these is given

The cleanroom case study in the Software Engineering Laboratory: Project description and early analysis

This case study analyzes the application of the cleanroom software development methodology to the development of production software at the NASA/Goddard Space Flight Center. The cleanroom methodology emphasizes human discipline in program verification to produce reliable software products that are right the first time. Preliminary analysis of the cleanroom case study shows that the method can be applied successfully in the FDD environment and may increase staff productivity and product quality. Compared to typical Software Engineering Laboratory (SEL) activities, there is evidence of lower failure rates, a more complete and consistent set of inline code documentation, a different distribution of phase effort activity, and a different growth profile in terms of lines of code developed. The major goals of the study were to: (1) assess the process used in the SEL cleanroom model with respect to team structure, team activities, and effort distribution; (2) analyze the products of the SEL cleanroom model and determine the impact on measures of interest, including reliability, productivity, overall life-cycle cost, and software quality; and (3) analyze the residual products in the application of the SEL cleanroom model, such as fault distribution, error characteristics, system growth, and computer usage

Particle and microbial airborne dispersion from people

The airborne dispersion of particles from 55 people (30 females and 25 males) was measured. The dispersion per minute of microbe carrying particles (MCPs) averaged 2,400 when wearing personal indoor clothing, and 177 when wearing cleanroom garments. One exceptional person, whose dispersal rates were not included in these results, dispersed 11,000 per minute when wearing cleanroom garments. The dispersion rate of particles ≥5μm per minute averaged 332,000 when wearing indoor clothing, and 37,300 when wearing cleanroom garments. The dispersion rate of particles ≥0.5μm per minute averaged 2,130,000 when wearing indoor clothing, and 1,020,000 when wearing cleanroom garments. The dispersion rates for particles and MCPs were higher in males than females. Depending on the method used, the average equivalent particle diameter of the MCPs was 9μm or 18μm. There was no situation where the dispersion of MCPs was not accompanied by substantial numbers of both ≥0.5μm and ≥5.0μm airborne particles, and there appears to be little advantage in measuring particles ≥5.0μm when using airborne particle counting to indirectly monitor the dispersion of MCPs. When wearing cleanroom garments, the ratio of ≥0.5μm particles to MCPs was found to average 5,800:1, and for ≥5.0μm particles it was 210:1

Decay of airborne contamination and ventilation effectiveness of cleanrooms

This article reports an investigation into the ability of the air supply in non-unidirectional cleanrooms to aid recovery from episodes of airborne contamination, and minimise airborne contamination at important locations. The ISO 14644-3 (2005) recovery test, which measures the rate of decay of test particles, was assessed and a reinterpretation of the test results suggested. This allowed air change effectiveness indexes to be calculated and used to evaluate the ventilation effectiveness of the cleanroom’s air supply. Air change effectiveness indexes were measured in various designs of cleanrooms, and reasons for deviations in the value of the indexes investigated

Removal of microbe-carrying particles by high efficiency air filters in cleanrooms

The removal efficiency of high efficiency air filters against microbe-carrying particles (MCPs) in the air supply of occupied rooms, such as cleanrooms, was determined. Knowing the size distribution of MCPs in the air to be filtered, and the removal efficiency of a filter against individual particle diameters, the overall removal efficiency was ascertained. A variety of filters were investigated, and it was found that a filter 90% efficient, when tested against sub-micrometre particles, used in standard classification methods such as EN 1822, was greater than 99.99% efficient in removing MCPs. The effect of filter efficiency on the quality of the air supply, and the concentration of MCPs in cleanroom air was also studied. No practical improvement in airborne concentrations was obtained by filters that had a removal efficiency greater than 99.99% against MCPs. Use of a filter suitable for removing MCPs, rather than sub-micrometre particles, would give a reduction of about 6 to 8-fold in the pressure drop over a filter, and a substantial reduction in the cost of running a cleanroom

Collection efficiency of microbial methods used to monitor cleanrooms

Microbiological sampling methods used in pharmaceutical cleanrooms should efficiently collect and count microorganisms. Methods are described in this paper that allow collection efficiencies to be determined and maximised, and comparisons to be made between sampling methods

Microbial risk assessment in pharmaceutical cleanrooms

The microbial risk to aseptically manufactured products in pharmaceutical cleanrooms can be assessed by the use of fundamental equations that model the dispersion, transfer and deposition of microbial contamination, and the use of numerical values or risk descriptors. This can be done in two-stages, with the first stage used to assess the transfer of contamination from all of the sources within the cleanroom suite and the second stage used to assess both air and surface contact contamination within critical production areas. These two methods can be used to assess and reduce microbial risk at the preliminary design stage of the cleanroom and associated manufacturing process or, retrospectively, for an established manufacturing operation

Assessing microbial risk to patients from aseptically manufactured pharmaceuticals

The microbial risk to patients from aseptically manufactured pharmaceuticals is dependent on the chance that a product contains sufficient microbes to initiate an infection. This possibility is dependent on risk factors associated with the method of production and product formulation, and can be calculated. An analysis of these risk factors can be used to minimise patient risk and assist in determining the appropriate level of contamination control required for manufacturing

Removal efficiency of high efficiency air filters against microbe-carrying particles (MCPs) in cleanrooms

The removal efficiency of high efficiency air filters was determined against microbe-carrying particles (MCPs) in the air supply to cleanrooms. Knowing the size distribution of MCPs in the air to be filtered, and the filter's removal efficiency against individual particle diameters, the overall removal efficiency was ascertained. The removal efficiency of individual species of microbes with a known size was also obtained. A variety of filters were investigated, and it was found that a filter 90% efficient against the most penetrating particle size (as classified by EN 1822) was greater than 99.99% efficient in removing a MCPs. The effect of filter efficiency on the microbial concentration in both the air supply and the cleanroom air was studied, and no practical improvement in the air quality was obtained by filters that had a removal efficiency greater than 99.99% against MCPs. Use of a filter suitable for removing MCPs, rather than sub-micrometre particles, would give a reduction of about 6 to 8-fold in the pressure differential across the filter, and a substantial reduction in the energy costs of running a cleanroom