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

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

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

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

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

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

Microbiological contamination models for use in risk assessment during pharmaceutical production

This paper describes the fundamental mechanisms of microbial contamination during manufacture of pharmaceutical products. Models are derived that describe air and surface contact contamination. These models can be used to develop and improve methods of microbial risk assessment. The use of the FMEA (FMECA) method of risk assessment is discussed and, when used with the correct risk factors, its use endorsed

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