Effective Airflow Visualization Studies - PharmOut · Airflow Visualization Studies – Guidelines 1. Have written objectives for each visualization study. 2. Even if studies are

Slide 1 © PharmOut 2017

Effective Airflow Visualization Studies

Gordon Farquharson, July 2017


Agenda

• Regulatory imperative

• Role of CFD

• Air velocity measurements

• Airflow visualisation to prove effectiveness of airflow


Regulatory Imperative


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.


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• EU and PIC/S Guidance is very limited by comparison, and is quite out of date in relation to normal practice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.


Air flow visualisation testsOnly applicable in UDAF systems


Unidirectional Airflow – Side return

The linked problems – Measuring velocity & proving effectiveness

Turbulent Vortex risk area

Velocity at

working height



CFD for UDAF Systems


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.


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.


3D Illustration of the Lyophiliser problem

UDF Grade A

Non- UDF Grade B

Top of Lyodoor

Grade A AGV adjacent to

“Pizza” opening


• 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.

CFD Grid Illustration


Vector Illustration



100% Ceiling coverage





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.


Airflow visualisation studies

© Critical Systems Ltd 2016

November 2016


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.


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.



Example poor airflow in an isolator


Example improved airflow in Isolator experiment


Thank you for your time.Questions?

Gordon Farquharson

[email protected]

www.pharmout.net

Executive Consultant


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Effective Airflow Visualization Studies - PharmOut · Airflow Visualization Studies – Guidelines 1. Have written objectives for each visualization study. 2. Even if studies are