Monday, 7 October 2013

Air Flow Visualization (smoke test) and contamination control - FDA's inspectional observations (483's)


“Air flow visualization studies are intended to demonstrate visual evidence of air flow direction. The test helps to identify stagnant areas within a clean room; these areas can further act as a channel or reservoir of contaminants. The test can also be used to demonstrate the effects on airflow caused by equipment”.


The predominant sources of contaminants within a clean room are people and machinery. Air flow patterns in the clean zones can be easily disturbed by the factors such as machine guarding, equipment design, inappropriate component specifications or necessary interventions. These factors can altogether contributes to a higher potential risk of air borne contamination.

FDA and regulatory agencies in the EU ask for documented studies about air flows in critical zones under dynamic conditions. Turbulence and stagnant air can act as a channel or reservoir for the accumulation of air borne contaminants.

Smoke studies provides visual evidence of air flow direction. If a particle or air born contaminant  enters a clean room, the smoke test will demonstrate where the particle will likely move. 

Desired airflow characteristics in clean room are 

1.Air flow move toward potential sources of contamination and away from the product path. Ex:HEPA  filtered air should not flow over clean room personnel and then over the product path.

2.Air should be flowing smoothly in one direction with no turbulence or eddies.

3. For movement within the air stream, such as a person manipulating materials or product, air disruption should recover quickly to regain unidirectional flow.



WHO GMP For Sterile Pharmaceutical Products Working document QAS/09.295 Rev.1

“Grade A: The uniformity and effectiveness of the unidirectional flow shall be demonstrated by undertaking airflow visualization tests”

EU GMP Annex 1
“It should be demonstrated that air-flow patterns do not present a contamination risk, e.g. care should be taken to ensure that air flows do not distribute particles from a particle generating person, operation or machine to a zone of higher product risk”.

Pharmaceutical Inspection Convention (PIC/S)GMP Annex 1 Revision 2008 Interpretation Of Most Important Changes For The Manufacture Of Sterile Medicinal Products -Recommendation January 2010
“Non-viable particles should be measured and are expected to meet grade A requirements. Smoke studies should be performed.”

FDA Guidance  Document” Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice” (September 2004)
Proper design and control prevents turbulence and stagnant air in the critical area. Once relevant parameters are established, it is crucial that airflow patterns 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 have been found to be useful aides 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.

Airflow patterns are highly sensitive and easily altered by everyday occurrences; this disruption can compromise product quality. Since unidirectional air flow in a clean room plays a major role in contamination control, the FDA inspectors pays more attention to the videotaped air flow visualization studies. The number of 483’s issued to pharmaceutical manufacturers in recent years strongly supports this statement.

FDA’s Inspectional Observations (483’s) on  Air Flow Pattern Visualization
1.Smoke studies in ISO 5 hoods were not conducted under dynamic conditions.
2. There has been no air flow pattern (i.e smoke study) evaluation study performed to determine the acceptability of the horizontal air flow, that is, the air flow is not compromised (i.e air turbulence/air eddies) during the aseptic operations that are performed in the ISO-5 area.
3. There has been no air flow pattern evaluation to determine that the personnel activities and manual transfer of materials between the ISO-8 and ISO-7 areas negatively affect the air movement and air cascade.
4. Smoke studies  have not been properly documented for the air flow patterns of the ISO 6 class rooms or  ISO 5  laminar air flow hoods used in the processing of injectable products.
5. The air flow pattern video does not present data to adequately assess the requested “downward sweeping air flow pattern” for the ISO 5 aseptic fill zone. The firm failed to evaluate the potential product impact of the turbulence, air eddies observed in the middle of the ISO 5 hoods  during dynamic operations.
6.Smoke study did not include an evaluation of the personnel activities performed in the  adjacent ISO 5 hoods to determine that the personnel activities do not negatively affect air flow patterns within ISO 5 hoods.
7. The smoke study does not demonstrate critical aseptic connections performed during the assembly of ISO 5 hoods used to fill sterile pharmaceuticals.

In any environment where human operators are involved ,microbial contamination is inevitable .Carefully designed ventilating  system and operating  practices  can protect the product from contamination risks to some extent. Airflow visualization helps to diagnose problems such as excess contamination build up in clean room.



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