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Airflow visualisation: In an aseptic facility

Article · May 2012

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Tim Sandle
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 HVAC

Airflow
ecause a cleanroom is designed to

B 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
visualisation
measurement of physical parameters, e.g.
airflow rates, for critical operations such as
aseptic filling, a visualisation of the air
movement is required.1
in an aseptic facility
Knowing how air moves in a cleanroom or
clean air device is important to help
Airflow visualisation is a useful method for risk
understand how the air affects any assessment of pharmaceutical processing.
contamination that might be present. This
can be achieved through airflow Dr Tim Sandle*, from the Pharmaceutical
visualisation studies.
A successful airflow design has two
Microbiology Interest Group (Pharmig),
F
aspects for consideration: effective demonstrates how, using an airflow study at a
contamination control in the cleanroom;
and efficient delivery of air to the cleanroom. filtration transfer activity in an aseptic filling facility
O
To maintain effective contamination control
for a particular cleanroom, a large quantity of Airflow studies can provide a significant Airflow studies are normally performed
cleaned air is often needed. amount of information. They can help in using a smoke pencil or a smoke generator,
assessing whether airflows are drawing depending upon how much smoke is needed
O

Efficiency factors potentially contaminated air towards a for the study. The amount required relates to
The following major factors will have a role in critical zone or whether certain objects in the the equipment or process that is being
determining the air system efficiency: clean- air-stream cause contamination by forcing examined. The air direction and air velocity
PR

room activities (relating to the processes that the air to change direction. should be noted.
take place within the cleanroom and the In addition the analysis of the results The following list outlines the type of
cleanliness class of the cleanroom), airflow obtained can be beneficial in the selection of scenarios that could be examined when
rate, airflow distribution (such as turbulent sample sites and frequencies and in refining conducting airflow studies and why:
or unidirectional flow), particle size, particle personnel procedures and materials flow in ● To demonstrate the difference between
transport rate, and HVAC equipment and aseptic processing. Such studies can form static and dynamic states and the direction
components (such as the type and efficiency part of the risk assessment of pharma- of laminarity away from the critical zone
of the HEPA filter).2 ceutical processing.3 ● To demonstrate the impact of operator 䊳

Figure 1: Diagram of filtration transfer in the filtration room

The stronger airflows are represented by the thicker arrows. As illustrated in the diagram above, there is a strong airflow away from transfer
ports and no dead spots, airflow is constant. The airflow over the transfer port was generally in a horizontal unidirectional pattern

www.cleanroom-technology.co.uk May 2012 CLEANROOM TECHNOLOGY 27

 HVAC

䊳
interventions and other personnel activity A further issue to consider is the The airflow study was conducted at an
● To show the impact of equipment subsequent examination and reporting of aseptic filling manufacturing plant in the UK.
operating airflow studies. The following example of a The activity examined was the sterile
● To demonstrate the set-up of equipment filtration transfer activity in an aseptic filling filtration of a product from outside the
● To determine if a unidirectional airflow is facility demonstrates how an airflow study aseptic area into a sterile vessel contained
present (if required). Where this is the case, it can be reported. During the study the within the facility. The room in which the
is important to establish whether the airflow placement of samples for the monitoring of transfer took place was a Grade B
is smooth, free from disturbances (such as the environment was also noted.5 (ISO class 7) room. The critical activity was
small, temporary vortices or eddies) and the connection of the transfer line to the
unimpeded Airflow study example vessel using sterile tubing fitted with sterile
● Where a turbulent flow is expected (an air- Before undertaking an airflow study it is connectors. The connection activity took

F
pattern characterised by small and important to decide on the acceptance place within an air-stream protected by a
temporary fluctuations caused by criteria and to document this. It is unidirectional airflow from a mobile UDAF
instabilities) the impact of any air eddying additionally useful to rehearse the study unit.

O must be examined to note any effect upon

critical process steps.
beforehand and to ensure, especially if
studies are carried out in production
shutdowns, that those involved are wearing
The unidirectional airflow is a key
parameter of a clean air device in terms of
the air velocity (operating at 0.45 metres per
O
Vortex regions the appropriate clothing and are behaving in second (±20%) and air direction. The object
Outside of unidirectional airflow (UDAF) an appropriate cleanroom manner. of the unidirectional airflow is to push
units (such as an ISO class 7/Grade B
support room), missed airflow patterns are
PR

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 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 Figure 2: Photograph showing the layout for the filtration activity in the filtration room
perpendicular to the airflow. The air-velocity (Aseptic Filling Suite)
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. Figure 3: Photograph showing that there is a strong, horizontal, fast moving air-flow across
These different factors have an impact on the face of the UDAF and the transfer port. Therefore any contamination arising from the
airflow study design and execution. activity or from the operative is unlikely to remain in the vicinity

28 CLEANROOM TECHNOLOGY May 2012 www.cleanroom-technology.co.uk

 HVAC

outward any contamination that might be Following the completion of the study the cleanroom understands where these ‘dead
deposited into the air-stream and to avoid room was cleaned and disinfected so that spots’ can occur and then either attempts to
the potential for contamination dropping any residues of the smoke were removed engineer these out or undertakes a suitable
out of the air, either through gravity or by from equipment and cleanroom surfaces. risk assessment or targets environmental
striking an object, and falling onto a critical On completion of the airflow study it was monitoring samples (viable and particulate
surface. transferred to permanent media and monitoring) towards the areas of concern.6 It
reviewed. The review included a short, is also important to re-assess airflow studies
Study result documented report about the outcome. following any changes to room design or to
A smoke generator was used to perform the In conclusion, the airflow in relation to the the HVAC system. Some organisations
airflow study and a simulation of the filtration transfer simulation at the critical choose to repeat airflow studies at regular
filtration activity was carried out using location was quite rapid (indicating that the intervals.

F
trained staff. The smoke generator and UDAF unit was supplying air at a high This example demonstrated the
digital capture devices were operated by velocity) and the airflow over the transfer importance of airflow studies as a means to
trained pharmaceutical microbiologists. The port was generally in a horizontal direction, understand visually the airflow within a

O
study was captured on video tape and using indicating a unidirectional pattern. Neither cleanroom.
digital images. The activity lasted the activity nor the personnel disrupted or Airflow visualisation studies form an
approximately 15 minutes.
O interfered with the airflow during the important part of contamination control and
Figures 1–3 indicate a possible approach simulation and there was no indication of air can be used both proactively, to put in place
that can be taken for the examination of from the less clean area entering the critical measures to prevent contamination from
airflow studies in terms of the study zone. The air pattern was therefore occurring or to confirm that an area is in
preparation; simulated activity and the way satisfactory. control, or they can be used reactively in
PR
in which the results can be examined and Should problematic airflow patterns response to an out-of-limits result
reported. occur, it is important that the manager of the investigation. CT

References
CONTACT
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. *Dr Tim Sandle is Head of Microbiology,
3. Ljungquist, B. and Reinmuller, B. (2001): Microbiological Risk Assessment in Pharmaceutical Clean Rooms, Parenteral Drug
Association: USA.
BPL and chairman of the Pharmaceutical
4. Klinberg, S. Journal of Validation Technology, Summer 2010, pp11–17. Microbiology Interest Group (Pharmig) LAL
5. Sandle, T. ‘Environmental Monitoring’ in Saghee, M.R., Sandle, T. and Tidswell, E.C. (Eds.) Microbiology and Sterility Assurance in action group
Pharmaceuticals and Medical Devices, New Delhi: Business Horizons, 2011, pp293–32. ● Tim.Sandle@bpl.co.uk
6. Katayama H et al. (2005), PDA J Pharm Sci Technol, Vol. 59, No. 1, pp49–63.
● www.pharmig.org.uk

www.cleanroom-technology.co.uk May 2012 CLEANROOM TECHNOLOGY 15

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