A critical area is one in which the sterilized drug product, containers, and closures are exposed to environmental conditions designed to preserve sterility. Activities conducted in this area include manipulations (e.g., aseptic connections, sterile ingredient additions) of sterile materials prior to and during filling and closing operations.
This area is critical because the product is not processed further in its immediate container and is vulnerable to contamination. In order to maintain product sterility, the environment in which aseptic operations are conducted should be of appropriate quality throughout operations. One aspect of environmental quality is the particulate content of the air. Particulates are significant because they can enter a product and contaminate it physically or, by acting as a vehicle for microorganisms, biologically. Particle content in critical areas should be minimized by effective air systems.
Air in the immediate proximity of exposed sterilized containers/closures and filling/closing operations is of acceptable particulate quality when it has a per-cubic-foot particle count of no more than 100 in a size range of 0.5 microns and larger (Class 100) when counted at representative locations normally not more than one foot away from the work site, within the airflow, and during filling/closing operations. Deviations from this critical area monitoring parameter should be documented as to origin and significance.
Measurements to confirm air cleanliness in aseptic processing zones should be taken with the particle counting probe oriented in the direction of oncoming airflow and at specified sites where sterilized product and container-closure are exposed. Regular monitoring should be performed during each shift. Nonviable particulate monitoring with a remote counting system is generally less invasive than the use of portable particle counting units and provides the most comprehensive data.
Some powder filling operations can generate high levels of powder particulates that, by their nature, do not pose a risk of product contamination. It may not, in these cases, be feasible to measure air quality within the one foot distance and still differentiate "background noise" levels of powder particles from air contaminants. In these instances, air should be sampled in a manner that, to the extent possible, characterizes the true level of extrinsic particulate contamination to which the product is exposed. Initial certification of the area under dynamic conditions without the actual powder filling function should provide some baseline information on the non-product particle generation of the operation.
Air in critical areas should be supplied at the point of use as HEPA filtered laminar flow air at a velocity sufficient to sweep particulate matter away from the filling/closing area and maintain laminarity during operations. The velocity parameters established for each processing line should be justified, and appropriate to maintain laminarity and air quality under dynamic conditions within a defined space.
Proper design and control should prevent turbulence or stagnant air in the aseptic processing line or clean zone. Once relevant parameters are established, airflow patterns should be evaluated for turbulence. Air pattern or smoke studies demonstrating laminarity and sweeping action over and away from the product under dynamic conditions should be conducted. The studies should be well-documented with written conclusions. Videotape or other recording mechanisms have been found to be useful in assessing airflow initially as well as facilitating evaluation of subsequent equipment configuration changes. However, even successfully qualified systems can be compromised by poor personnel, and operational, or maintenance practices.
Active air monitoring of critical areas should normally yield no microbiological contaminants. Contamination in this environment should receive investigative attention.
Ankur Choudhary is an experienced pharmaceutical blogger.