Critical Area – Class 100 (ISO 5) AS PER USFDA GUIDELINE
A critical area is one in which the sterilized drug product, containers, and closures are exposed to
environmental conditions that must be designed to maintain product sterility (§ 211.42(c)(10)).
Activities conducted in such areas include manipulations (e.g., aseptic connections, sterile ingredient additions) of sterile materials before and during filling and closing operations.
This area is critical because an exposed product is vulnerable to contamination and will not be
subsequently sterilized in its immediate container.To maintain product sterility, the environment in which aseptic operations (e.g., equipment setup, filling) are conducted must be controlled and maintained at an appropriate quality.
One aspect of environmental quality is the particle content of the air. Particles are significant because they can enter a product as an extraneous contaminant, and can also contaminate it biologically by acting as a vehicle for microorganisms. Appropriately designed air-handling systems minimize particle content of a critical area.
Air in the immediate proximity of exposed sterilized containers/closures and filling/closing operations would be of appropriate particle quality when it has a per-cubic-meter particle count of no more than 3520 in a size range of 0.5 µm and larger when counted at representative locations normally not more than 1 foot away from the work site, within the airflow, and during filling/closing operations. This level of air cleanliness is also known as Class 100 (ISO 5).
Guideline recommends that measurements to confirm air cleanliness in critical areas be taken at sites
where there is most potential risk to the exposed sterilized product, containers, and closures.
The particle counting probe should be placed in an orientation demonstrated to obtain a meaningful
sample. Regular monitoring should be performed during each production shift.
Guideline recommend conducting nonviable particle monitoring with a remote counting system. These systems are capable of collecting more comprehensive data and are generally less invasive than portable
particle counters.
Some operations can generate high levels of product (e.g., powder) particles 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 levels of particles from air contaminants. In these instances, air can be sampled in a manner that, to the extent possible, characterizes the true level of extrinsic particle contamination to which the product is exposed.
Initial qualification of the area under dynamic conditions without the actual filling function provides some baseline information on the non-product particle generation of the operation.
HEPA-filtered air should be supplied in critical areas at a velocity sufficient to sweep particles away from the filling/closing area and maintain unidirectional airflow during operations. The velocity parameters established for each processing line should be justified and appropriate to maintain unidirectional airflow and air quality under dynamic conditions within the critical area.
Note- A velocity of 0.45 meters/second (90 feet per minute) has generally been established, with a range of plus or minus 20 percent around the setpoint. Higher velocities may be appropriate in operations generating high levels of particulates.
Also, read – VALIDATION OF ASEPTIC PROCESSING AS PER USFDA GUIDELINE
Proper design and control prevent turbulence and stagnant air in the critical area. Once relevant parameters are established, airflow patterns must be evaluated for turbulence or eddy currents that can act as a channel or reservoir for air contaminants (e.g., from an adjoining lower classified area).
In situ, air pattern analysis should be conducted at the critical area to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions. The studies should be well documented with written conclusions, and include evaluation of the impact of aseptic manipulations (e.g., interventions) and equipment design. Videotape or other recording mechanisms are useful aids in assessing airflow initially as well as facilitating evaluation of subsequent equipment configuration changes.
It is important to note that even successfully qualified systems can be compromised by poor operational, maintenance, or personnel practices.
Air monitoring samples of critical areas should normally yield no microbiological contaminants.
The guideline recommends affording appropriate investigative attention to contamination occurrences in this
environment.
