Slide 1 © PharmOut 2017

Common mistakes

Cleanroom HVAC Design & Execution

Gordon Farquharson, July 2017

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Agenda

• Sources - Experiences

• Documentation integrity

• Room pressure balancing & control

• HEPA filter problems

• Managing alerts, alarms and adverse events.

• BAS and CSV issues

Sources - Experience

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Sources and Objectives

• Sources of information and experience for this presentation are:

• Design Experience.

• Design Review & DQ outputs.

• Expert witness/investigation.

• Project “lessons learned” reviews.

• My Objectives:

• To identify some key risk areas.

• Focus on root cause.

• Help avoid pitfalls.

• DQ and DR guidance.

Documentation integrity

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Documentation problems

• Lack of clear objectives – No URS or poor URS.

• Rationale for design decisions not recorded.

• Sometimes why we didn’t do something is as important as why we did do it. e.g. No silent hour set-back due to risk associated with increased complexity.

• As installed records incorrect/incomplete.

• Drawings.

• Commissioning data.

• Poor or no hand-over (turn-over) document set.

• Post installation changes, physical & commissioning, not recorded.

• Non-GMP technical design files:

• Not well documented.

• Don’t exist, or not retained.

• Not checked/approved by the engineering quality system.

Room Pressure –Balancing & Control

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Room pressure problems

• Failure to think through the regime and steps carefully.

• Didn’t consider the impact of process equipment – lack of information, knowledge and experience.

• Cleanroom leaked more than we expected; needed excessive pressurisation air; leading to dehumidification and pressure achievement problems.

• Leakage reliance on fragile door seals which fail and increase door leakage..

• Manual balancing dampers inaccessible; making balancing almost impossible.

• Automated balancing system unstable.

• Control loops not tuned properly.

• Conflict between control loops.

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Room pressure – Process equipment

• Tunnel has a max Dp tolerance, usually 30-40 Pa.

• In-flow volume varies with status of machine:

• OFF; Standby; start-up loading; shut-down unloading.

• Cleanroom or Isolator design must allow or compensate for these changes. Must be commissioned and qualified.

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Room leakage

The problem:

• Not known; inadequate estimated allowance made.

• Installation quality not controlled or tested.

• Get a big surprise during commissioning.

The solution:

• Select or specify an enclosure integrity.

• Make allowance in HVAC design.

• Test sample or all rooms for installed integrity.

• Check airflow balance as part of HVAC commissioning.

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Image courtesy of Bovis Lend Lease

Pressure Hold Test Apparatus

Test being applied to ACDP CL3 and SAPO 4 Containment facilities.

Notice the blank door used for this test, with pressure tapping connected to the test apparatus.

This test was used to prove compliance with a leakage rate specified in accordance with AS/NZS 2243.3-2002 . The test was carried out in accordance with the principles specified in ASTM : E 779 – 03

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Door seals

• Do you need them?

• Ensure they are robust and not easily damaged.

• The devil is in the detail.

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Impossible to balance and regulate

• 1.2 m ceiling void, accessed through ceiling access doors.

• Ceiling void contained manual room pressure balancing dampers; constant volume regulators; and tight shut-off dampers.

• Also, multiple examples of very bad installation practice; like the distorted flexible duct.

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Automated pressure control unstable

• Sophisticated BAS controlled system.

• PID control loops.

• Auto damper hunting leads to Dp varying +/- 7 to 10 Pa around set-point.

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Airflow Control Dampers – Linear control authority is essential

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Terminal HEPA Filter issues

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HEPA filter & leak testing issues

• Filters and housings poorly specified and controlled.

• No practical plan and installation of filter testing points –aerosol injection & testing of duct mounted filters in safety applications always the biggest problem.

• Lack of understanding and control of in-situ filter leak testing:

• So called “bleed-through”.

• Control of aerosol size distribution.

• Understanding Photometer vs Particle counter test methods.

• No policy on managing filter leaks – severity, frequency, cause, prediction.

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Local & Overall Penetration/EfficiencyEN 1822 H 14 HEPA

Overall penetration< 0.005 % @ MPPS

Local pen< 0.025 %

Local pen< 0.025 %

Local pen< 0.025 %

@ MPPS0.2 m

No limit to number of local leaks, butLocal & Overall Pen % must pass the limits.

Challenge is set to 100%

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Local & Overall In-situ Leak Test - H 14 HEPA

Local pen< 0.01 %

Local pen< 0.01 %

Local pen< 0.01 %

PAO aerosol & photometer

100% Upstream challenge (20-80 mg/litre PAO)

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Impossible to test and service

• No aerosol injection and down-stream test points installed.

• Filter housing impossible location for a safe “bag-out” filter change.

• Why did this happen?

• Poor conceptual design, not enough space.

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Filter leak testing options

• Revised ISO 14644-1, Cleanrooms and associated controlled environments – Part 3: Test Methods, will include more balanced specification for in-situ filter leak testing.

• Photometer method.

• Using a PAO challenge.

• Particle counter method.

• Using a PAO, PSL, or natural aerosol challenge.

• Requires much lower concentration.

• More susceptible to background induction.

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Leak testing in-line filters

Automated face scan using particle counter system – MPPS, rapid and minimal access intervention required.

Courtesy Camfil-Farr

Manual Photometer Face-scan using an adapted bag-out section.

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Practical Instrument – Leak testing using a particle counter

• Adapted particle counter can evaluate “rate of count” . Means that testing can be very similar to a photometer that measures concentration of an aerosol.

• Images courtesy of Lighthouse

And finally – some BAS & CSV issues

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Building automation system issues

• How to take advantage of increasingly comprehensive system capability.

• Control & Monitoring – separate or combined.

• Making the CSV decision – IN or OUT of the validation bucket.

• Poor hardware architecture makes life more complex.

• Separate outstations for GMP & non-GMP systems.

• No discrimination of criticality of information, alerts and alarms.

• Everything referred to QA imposes an unnecessary burden.

• Discriminate – Engineering Alert/Alarm; GMP/QA Alert/Alarm; and remember to look at trending including frequency of occurrences.

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Thank you for your time.Questions?

Gordon Farquharson

gordon.farquharson@pharmout.net

www.pharmout.net

Executive Consultant

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