Airflow visualisation is a useful method for risk assessment of pharmaceutical processing. Dr Tim Sandle, from the Pharmaceutical Microbiology Interest Group (Pharmig), demonstrates how, using an airflow study at a filtration transfer activity in an aseptic filling facility.
Because a cleanroom is designed to control the concentration of airborne particles, a large amount of clean (filtered) air is required to remove or dilute contaminants for satisfactory operations in a critical cleanroom environment. Although this is controlled through Heating, Ventilation and Air Conditioning (HVAC) systems and assessed through the measurement of physical parameters, e.g. airflow rates, for critical operations such as aseptic filling, a visualisation of the air movement is required.1
Knowing how air moves in a cleanroom or clean air device is important to help understand how the air affects any contamination that might be present. This can be achieved through airflow visualisation studies.
A successful airflow design has two aspects for consideration: effective contamination control in the cleanroom; and efficient delivery of air to the cleanroom. To maintain effective contamination control for a particular cleanroom, a large quantity of cleaned air is often needed.
Efficiency factors
The following major factors will have a role in determining the air system efficiency: cleanroom activities (relating to the processes that take place within the cleanroom and the cleanliness class of the cleanroom), airflow rate, airflow distribution (such as turbulent or unidirectional flow), particle size, particle transport rate, and HVAC equipment and components (such as the type and efficiency of the HEPA filter).2
Airflow studies can provide a significant amount of information. They can help in assessing whether airflows are drawing potentially contaminated air towards a critical zone or whether certain objects in the air-stream cause contamination by forcing the air to change direction.
In addition the analysis of the results obtained can be beneficial in the selection of sample sites and frequencies and in refining personnel procedures and materials flow in aseptic processing. Such studies can form part of the risk assessment of pharma-ceutical processing.3
Airflow studies are normally performed using a smoke pencil or a smoke generator, depending upon how much smoke is needed for the study. The amount required relates to the equipment or process that is being examined. The air direction and air velocity should be noted.
The following list outlines the type of scenarios that could be examined when conducting airflow studies and why:
- To demonstrate the difference between static and dynamic states and the direction of laminarity away from the critical zone
- To demonstrate the impact of operator interventions and other personnel activity
- To show the impact of equipment operating
- To demonstrate the set-up of equipment
- To determine if a unidirectional airflow is present (if required). Where this is the case, it is important to establish whether the airflow is smooth, free from disturbances (such as small, temporary vortices or eddies) and unimpeded
- Where a turbulent flow is expected (an air-pattern characterised by small and temporary fluctuations caused by instabilities) the impact of any air eddying must be examined to note any effect upon critical process steps.
Vortex regions
Outside of unidirectional airflow (UDAF) units (such as an ISO class 7/Grade B support room), missed airflow patterns are more typical. The biggest risk in these areas is when potential airborne particles could accumulate in vortex regions. This can happen when a unidirectional airflow strikes an object and creates a ‘wake region’. It is prudent to confirm the level of particles in such regions through the use of a discrete particle counter.
When a streamline meets an object and causes turbulence (or meets air that is turbulent), then contamination could potentially be dispersed
When examining airflows, the ‘streamlines’ of the air should be noted. A streamline is defined as the route that the air is taking and will be the path that any contamination by ventilation could take (so-called convective transport). When a streamline meets an object and causes turbulence (or meets air that is turbulent), then contamination could potentially be dispersed (so-called turbulent diffusion).
Regions of stagnation should also be noted. These can often occur in front of machinery and by work surfaces that are perpendicular to the airflow. The air-velocity in these areas can be unpredictable.4
Air velocity
Another factor to note is air velocity. For larger particles of air (such as those ≥100µm) then particular air-velocities can drive such particles downwards.
Problems that occur can be the result of:
- Heat rising from machinery and disrupting the airflow
- Obstructions preventing the supply of air reaching a critical area
- Obstructions or machinery design turning a unidirectional flow into a turbulent flow
- Entrainment, where contamination is drawn into clean air
- Stagnant or turbulent areas acting as conduits for entry of contamination
- When air flowing from personnel is directed towards the critical zone.
These different factors have an impact on airflow study design and execution. A further issue to consider is the subsequent examination and reporting of airflow studies. The following example of a filtration transfer activity in an aseptic filling facility demonstrates how an airflow study can be reported. During the study the placement of samples for the monitoring of the environment was also noted.5
Figure 3: Photograph showing that there is a strong, horizontal, fast moving air flow across the face of the UDAF and the transfer port. Therefore any contamination arising from the activity or from the operative is unlikely to remain in the vicinity
Airflow study example
Before undertaking an airflow study it is important to decide on the acceptance criteria and to document this. It is additionally useful to rehearse the study beforehand and to ensure, especially if studies are carried out in production shutdowns, that those involved are wearing the appropriate clothing and are behaving in an appropriate cleanroom manner.
The airflow study was conducted at an aseptic filling manufacturing plant in the UK. The activity examined was the sterile filtration of a product from outside the aseptic area into a sterile vessel contained within the facility. The room in which the transfer took place was a Grade B (ISO class 7) room. The critical activity was the connection of the transfer line to the vessel using sterile tubing fitted with sterile connectors. The connection activity took place within an air-stream protected by a unidirectional airflow from a mobile UDAF unit.
The object of the unidirectional airflow is to push outward any contamination that might be deposited into the air-stream and to avoid the potential for contamination dropping out of the air
The unidirectional airflow is a key parameter of a clean air device in terms of the air velocity (operating at 0.45 metres per second (±20%) and air direction. The object of the unidirectional airflow is to push outward any contamination that might be deposited into the air-stream and to avoid the potential for contamination dropping out of the air, either through gravity or by striking an object, and falling onto a critical surface.
Study result
A smoke generator was used to perform the airflow study and a simulation of the filtration activity was carried out using trained staff. The smoke generator and digital capture devices were operated by trained pharmaceutical microbiologists. The study was captured on video tape and using digital images. The activity lasted approximately 15 minutes.
Figures 1–3 indicate a possible approach that can be taken for the examination of airflow studies in terms of the study preparation; simulated activity and the way in which the results can be examined and reported.
Following the completion of the study the room was cleaned and disinfected so that any residues of the smoke were removed from equipment and cleanroom surfaces. On completion of the airflow study it was transferred to permanent media and reviewed. The review included a short, documented report about the outcome.
In conclusion, the airflow in relation to the filtration transfer simulation at the critical location was quite rapid (indicating that the UDAF unit was supplying air at a high velocity) and the airflow over the transfer port was generally in a horizontal direction, indicating a unidirectional pattern. Neither the activity nor the personnel disrupted or interfered with the airflow during the simulation and there was no indication of air from the less clean area entering the critical zone. The air pattern was therefore satisfactory.
Should problematic airflow patterns occur, it is important that the manager of the cleanroom understands where these ‘dead spots’ can occur
Should problematic airflow patterns occur, it is important that the manager of the cleanroom understands where these ‘dead spots’ can occur and then either attempts to engineer these out or undertakes a suitable risk assessment or targets environmental monitoring samples (viable and particulate monitoring) towards the areas of concern.6 It is also important to re-assess airflow studies following any changes to room design or to the HVAC system. Some organisations choose to repeat airflow studies at regular intervals.
This example demonstrated the importance of airflow studies as a means to understand visually the airflow within a cleanroom.
Airflow visualisation studies form an important part of contamination control and can be used both proactively, to put in place measures to prevent contamination from occurring or to confirm that an area is in control, or they can be used reactively in response to an out-of-limits result investigation.
References
1. Schneider, R. (2001): American Society of Heating, Refrigerating and Air-Conditioning Engineers Journal, Vol. 43 (8): 39–46.
2. Whyte, W. (1999). Cleanroom Design, 2nd Edition. John Wiley & Sons: Chichester.
3. Ljungquist, B. and Reinmuller, B. (2001): Microbiological Risk Assessment in Pharmaceutical Clean Rooms, Parenteral Drug Association: USA.
4. Klinberg, S. Journal of Validation Technology, Summer 2010, pp11–17.
5. Sandle, T. ‘Environmental Monitoring’ in Saghee, M.R., Sandle, T. and Tidswell, E.C. (Eds.) Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices, New Delhi: Business Horizons, 2011, pp293–32.
6. Katayama H et al. (2005), PDA J Pharm Sci Technol, Vol. 59, No. 1, pp49–63.
