Effective Airflow

Visualization Studies

Gordon Farquharson, July

2017

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Agenda

• Regulatory imperative
• Role of CFD
• Air velocity measurements
• Airflow visualisation to prove effectiveness of airflow

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 Regulatory Imperative

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 UDAF Guidance – US FDA.
Industry uses this US guidance as a reference (2004 Aseptic guidance.

• US FDA’s guidance really says it all. If you’re unfamiliar I suggest you

read it carefully.
• 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.

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UDAF Guidance – Annex 1 EU & PIC/S
GMP

• EU and PIC/S Guidance is very limited by comparison,

and is quite out of date in relation to normal practice

• Recent EU inspections exhibit reported Critical & Major

Observations on inadequate airflow visualisation of Grade
A UDAF zone for aseptic processes.

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 Air flow visualisation tests
Only applicable in UDAF
systems

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 The linked problems – Measuring
velocity & proving effectiveness
Unidirectional Airflow – Side return

Velocity
at
working
height Turbulent Vortex
risk area
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 CFD for UDAF Systems

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Authors opinion/experience with CFD
• CFD - Computation Fluid Dynamics.
• Good design tool for applications that are too complex or
unusual to rely on prior experience.
• Computer software and modelling not easy to use – need
specialist skill and experience to develop a representative
model.
• Not a cheap process of evaluation, but can be good value in
context with the risk of getting it wrong.
• My experience:
• Unusual UDAF in aseptic processing.
• Critical environmental control in animal husbandry.
• Safety applications for handling hazardous biological and
chemical materials.
• Building discharges – an alternative to wind-tunnel tests.

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The Facility Requirements

• A Japanese Pharmaceutical Company was seeking to

optimise the design of a cleanroom containing vial filling
machines, lyophiliser loading and automated transport
systems.
• The GMP requirements were based primarily on the US
FDA 2004 APG recommendations for achieving effective
clean air protection of a critical aseptic process.

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3D Illustration of the Lyophiliser problem

Non- UDF
Grade B

UDF Grade A

Top of Lyo
door

Grade A AGV
adjacent to
“Pizza”
opening

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CFD Grid Illustration

• The physics of fluid flow, heat transfer and associated processes are
contained in the Navier-Stokes equation.
• Airflow modelling iteratively solves a simultaneous set of N-S
equations for spatial volume divided up into a number of finite cells.
The model can be solved for the airflow itself, and sources of heat and
other contaminants.

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Vector Illustration

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 100% Ceiling coverage

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 100% Ceiling coverage

50% Ceiling coverage

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 The Study Output = Results & Records
• Enabled reduction of the area of the uni-directional flow Grade A
cleanzone by 50%.
• This in turn enabled the total air volume required to ensure the correct
cleanroom cleanliness classes to be reduced by approximately 40% with
the consequent significant saving of installed plant and energy
consumption.
• Selection of the correct type of diffuser in the non-unidirectional flow
zone to ensure that the critical airflow is not disrupted.
• Resolution of the basic dimensions required inside the vial transport
system to avoid airflow updraft and vortex generation during vial
transfer to and from the lyophiliser.
• Allowed testing of the effect of temperature of supply air on the airflow.
Negative buoyancy can have a huge effect on UDAF effectiveness.
• Provided a clear guide as to where to focus testing effort during HVAC
system commissioning and flow visualization.

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 Airflow visualisation studies

© Critical Systems Ltd

2016
November 2016
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 Airflow Visualization Studies –
Guidelines

1. Have written objectives for each visualization study.

2. Even if studies are conducted during a shutdown, try to operate in
a production mode with personnel in full garb observing good
aseptic technique during a simulation.
3. Begin video taping the study by showing the equipment below the
ceiling level that is being washed by airflow and then pan up to
show the smoke at the ceiling.
4. Use a smoke source that is adequate to show good airflow.
5. Do not get too close to equipment with the smoke source. This can
cause smoke to display a turbulent action as it strikes flat surfaces.
6. Record all data at the time smoke studies are conducted. (time,
date, personnel present, room location, etc.)
7. Have clear acceptance criteria, and report against these.

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Airflow Visualisation Studies - Guidance

• Isothermal aerosol (smoke). Water

vapour or propylene glycol (glycerol).
• Should include operations and
interventions.
• Choreograph the visualisation.
• May need aids to improve optical
contrast.
• Pulsed aerosol source can help
visualise velocity.
• Multiple nozzles helps visualise
parallelism of flow.
• Frequency – At system qualification
and after significant system or process
change.
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Example poor airflow in an isolator

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Example improved airflow in Isolator
experiment

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Thank you for your time.
Questions?

Gordon Farquharson
www.pharmout.net

gordon.farquharson@pharmout.net
Executive Consultant

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