Cleanrooms have traditionally been classified using air cleanliness standards defined by the number of airborne particles. However, there is not always a correlation between the number of viable microorganisms and non-viable particles. While both particulate and microbial measurements are important, the effectiveness of the cleaning and sanitization procedures and the biological impact of personnel activities can best be measured by a microbial monitoring program.

There are a number of methodologies being used for sampling viable airborne microorganisms. Most common are the Slit-to-Agar Samplers, Sieve Impactors and Centrifugal Samplers which result in the measurement of viable organisms per volume of air. Settling plates are another simple, cost-effective way to gauge environmental control; however, USP cautions against using settling plate data as a strict quantitative measurement of microbial levels in the controlled environment.

Another valuable type of environmental monitoring is surface sampling using contact plates or swabs. There are many commercially available products that can simplify the sampling routine. When utilizing the contact plate method, it is imperative to remove all media traces after sampling with a disinfectant wipe to ensure the elimination of all residue from the sampling surface which could encourage bacterial growth. This method of testing directly measures the cleanliness of work surfaces and can also be used to document the effectiveness of cleaning procedures.

A general-purpose growth media such as Soybean Casein Digest Medium is appropriate for most monitoring programs. The selection of media may vary depending on other organisms of concern. For surface monitoring, the media should be supplemented with suitable additives to neutralize the effects of cleaning agents used on the sampled surfaces. If yeast and mold are of particular concern, Sabourauds Agar or Rose-Bengal Agar should also be included in the program.

When establishing a sampling plan, consideration must be given to the selection of sampling sites. Areas where product is exposed to air or surfaces are important locations to include in the sampling plan. Sampling frequency will be determined by the degree of risk associated with contamination levels at each sampling location. It is important that sampling be conducted during normal work activities.

A complete environmental monitoring program should include organism identification of the recovered flora. Knowledge of the types of organisms typically found can be most useful in conducting investigations of the source of contamination when action levels are exceeded or if sterility testing of product fails. Organism identification can be accomplished by either automated or classical methods.

Statistical evaluation of the sampling data should be utilized to establish alert and action limits. The data base size should be sufficient to evaluate whether or not the controlled environment is operating within an acceptable state of control. Trend analysis can be a valuable way to determine when negative changes are taking place, so that an investigation can be conducted and corrective action taken before products or processes are adversely impacted. While no one combination of sampling device, culture media and incubation conditions offers complete microbial information or correlates directly with cleanroom particle counts, a practical microbial monitoring program is a useful tool for assessing trends in environmental control and triggering action before a problem emerges.

An ISO committee on cleanrooms and controlled environments has issued guidance document, 14644-1: Cleanrooms and associated controlled environments Part 1: Classification of Cleanliness. A second document, 14644-2: Specifications for testing and monitoring to prove continued compliance, contains specifications for testing and monitoring. Their adoption as American National Standards will override the classifications specified in Federal Standard 209E. These documents provide additional information on environmental monitoring. -Anne Huffman Medical Device Testing Manager