Assessment of degree of risk from sources of microbial contamination in cleanrooms; 2: surfaces and liquids

The degree of risk from microbial contamination of manufactured products in healthcare cleanrooms has been assessed in a series of three articles. The first article discussed airborne sources, and this second article considers surface contact and liquid sources. A final article will consider all sources and give further information on the application of the risk method. The degree of risk to products from micro-organisms transferred from sources by surface contact, or by liquids, has been assessed by the means of fundamental equations used to calculate the likely number of microbes deposited (NMD) onto, or into, a product. The method calculates the likely product contamination rate from each source and gives a more accurate risk assessment than those presently available. It also allows a direct comparison to be made between microbial transfer by different routes, i.e. surface, liquid and air

Deposition velocities of airborne microbe-carrying particles

The deposition velocity of airborne microbe-carrying particles (MCPs) falling towards surfaces was obtained experimentally in operating theatres and cleanrooms. The airborne concentrations of MCPs, and their deposition rate onto surfaces, are related by the deposition velocity, and measurements made by a microbial air sampler and settle plates allowed deposition velocities to be calculated. The deposition velocity of MCPs was found to vary with the airborne concentration, with higher deposition rates occurring at lower airborne concentrations. Knowledge of the deposition velocity allows the deposition on surfaces, such as product or settle plates, by a known airborne concentration of MCPs to be predicted, as well as the airborne concentration that should not be exceeded for a specified product contamination rate. The relationship of airborne concentration and settle plate counts of MCPs used in Annex 1 of the EU Guidelines to Good Manufacturing Practice to specify grades of pharmaceutical cleanrooms was reassessed, and improvements suggested

Assessment of degree of risk from sources of microbial contamination in cleanrooms; 1: Airborne

The degree of risk from microbial contamination of manufactured products by sources of contamination in healthcare cleanrooms has been assessed in a series of three articles. This first article considers airborne sources, and a second article will consider surface contact and liquid sources. A final article will consider all sources and the application of the risk method to a variety of cleanroom designs and manufacturing methods. The assessment of the degree of risk from airborne sources of microbial contamination has been carried out by calculating the number of microbes deposited from the air (NMDA) onto, or into, a product from various sources. A fundamental equation was used that utilises the following variables (risk factors): concentration of source microbes; surface area of product exposed to microbial deposition; ease of microbial dispersion, transmission and deposition from source to product; and time available for deposition. This approach gives an accurate risk assessment, although it is dependent on the quality of the input data. It is a particularly useful method as it calculates the likely rate of product microbial contamination from the various sources of airborne contamination

Assessment of degree of risk from sources of microbial contamination in cleanrooms; 3: Overall application

A method of calculating the degree of risk of sources of microbial contamination to products manufactured in cleanrooms has been described in two previous articles. The degree of risk was ascertained by calculating the number of microbes deposited (NMD) onto, or into, a product from each source of contamination. The first article considered airborne sources, the second article considered surface and liquid sources, and this final article considers all three sources. The NMD method can be applied to various manufacturing methods and designs of cleanrooms but was illustrated by a vial-filling process in a unidirectional airflow (UDAF) workstation located in a non- UDAF cleanroom. The same example was used in this article to demonstrate how to control the microbial risk, and included the use of a restricted access barrier system. The risk to a patient is not only dependent on microbial contamination of pharmaceutical products during manufacture in cleanrooms and controlled zones but the chance that any microbes deposited in the product will survive and multiply during its shelf life, and this aspect of patient risk is considered

Calculation of air supply rates and concentrations of airborne contamination in non-UDAF cleanrooms

This article reviews a series of scientific articles written by the authors, where the following topics were investigated in relation to non-unidirectional airflow cleanrooms. (1) The air supply rate required to obtain a specified concentration of airborne contamination. (2) The calculation of concentrations of airborne contaminants in different ventilation and dispersion of contamination situations. (3) The decay of airborne contamination (a) during the ‘clean up’ test described in Annex 1 of the EU Guidelines to Good Manufacturing Practice (2008); (b) during the recovery rate test described in Annex B12 of ISO 14644-3 (2005); (c) associated with clean areas, such as airlocks, to reduce airborne contamination before a door into a cleanroom is opened. Worked examples are provided to demonstrate the calculation methods to provide solutions to the above topics

Calculation of airborne cleanliness and air supply rate for non-unidirectional airflow cleanrooms

Equations have been recently derived by Whyte, Lenegan and Eaton for calculating the airborne concentration of particles and microbe-carrying particles in non-unidirectional airflow cleanrooms. These equations cover a variety of ventilation systems, and contain the variables of air supply rate, airborne dispersion rate of contamination from machinery and people, surface deposition of particles from the air, concentration of contamination in fresh make-up air, proportion of fresh air, and air filter efficiencies. The relative importance of these variables is investigated in this present research paper, with particular regard to the removal efficiency, location, and number of air filters. It was shown that air filters were important in ensuring low levels of contamination in cleanrooms but the types of filters specified in current cleanroom designs were very effective in ensuring a minimal contribution to the cleanroom’s airborne contamination especially when a secondary filter is used in addition to a primary and terminal filter. The most important determinants of airborne contamination were the air supply rate and the dispersion rate of contamination within the cleanroom, with a lesser effect from deposition of airborne particles onto cleanroom surfaces. The information gathered confirmed the usefulness of the equation previously used by Whyte, Whyte, Eaton and Lenegan to calculate the air supply rate required for a specified concentration of airborne contamination

Microbial transfer by surface contact in cleanrooms

Experiments were carried out to ascertain the proportion of microbes that would be transferred from a contaminated surface to a receiving surface in a cleanroom. To simulate transfers, microbe-carrying particles (MCPs) were sampled from the skin onto donating sterile surfaces, which were latex gloves, stainless steel and clothing fabric. A contact was made between these surfaces and a sterile receiving surface of stainless steel, and the proportion of MCPs transferred ascertained. The proportion of MCPs transferred, i.e. the transfer coefficient, was 0.19 for gloves, 0.10 for stainless steel, and 0.06 for clothing fabric. These transfer coefficients would vary in different conditions and the reasons are discussed

Equations for predicting airborne cleanliness in non-unidirectional airflow cleanrooms

Equations are derived in this paper for predicting the airborne concentration of particles and microbe-carrying particles in non-unidirectional airflow cleanrooms during manufacturing. The equations are obtained for a variety of ventilation systems with different configurations for mixing fresh and recirculated air, air filter placements, and number and efficiency of air filters. The variables in the equations are air supply rate, airborne dispersion rate of contamination from machinery and people, surface deposition of particles from air, particle concentration in fresh makeup air, proportion of make-up air, and air filter efficiencies. The equations are amenable to relatively simple modification for the study of different cleanroom ventilation systems. The use of these equations to investigate the effect of different configurations of ventilation systems and the relative importance of the equation variables on airborne concentrations will be reported in a further paper

An analysis of bi-directional use of frequencies for satellite communications

The bi-directional use of frequencies allocated for space communications has the potential to double the orbit/spectrum capacity available. The technical feasibility of reverse band use (RBU) at C-band (4 GHz uplinks and 6 GHz downlinks) is studied. The analysis identifies the constraints under which both forward and reverse band use satellite systems can share the same frequencies with terrestrial, line of sight transmission systems. The results of the analysis show that RBU satellite systems can be similarly sized to forward band use (FBU) satellite systems. In addition, the orbital separation requirements between RBU and FBU satellite systems are examined. The analysis shows that a carrier to interference ratio of 45 dB can be maintianed between RBU and FBU satellites separated by less than 0.5 deg., and that a carrier to interference ratio of 42 dB can be maintained in the antipodal case. Rain scatter propagation analysis shows that RBU and FBU Earth stations require separation distances fo less than 10 km at a rain rate of 13.5 mm/hr escalating to less than 100 km at a rain rate of 178 mm/hr for Earth station antennas in the 3 to 10 m range