Common mistakes Cleanroom HVAC Design & Execution. Gordon Farquharson, July 2017

Transcription

1 Common mistakes Cleanroom HVAC Design & Execution Gordon Farquharson, July 2017 Slide 1 PharmOut 2017

2 Agenda Sources - Experiences Documentation integrity Room pressure balancing & control HEPA filter problems Managing alerts, alarms and adverse events. BAS and CSV issues Slide 2 PharmOut 2017

3 Sources - Experience

4 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. Slide 4 PharmOut 2017

5 Documentation integrity

6 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. Slide 6 PharmOut 2017

7 Room Pressure Balancing & Control

8 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. Slide 8 PharmOut 2017

9 Room pressure Process equipment Tunnel has a max Dp tolerance, usually 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. Slide 9 PharmOut 2017

10 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. Slide 10 PharmOut 2017

11 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 The test was carried out in accordance with the principles specified in ASTM : E Image courtesy of Bovis Lend Lease Slide 11 PharmOut 2017

12 Door seals Do you need them? Ensure they are robust and not easily damaged. The devil is in the detail. Slide 12 PharmOut 2017

13 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. Slide 13 PharmOut 2017

14 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. Slide 14 PharmOut 2017

15 15 Airflow Control Dampers Linear control authority is essential Slide 15 PharmOut 2017

16 Terminal HEPA Filter issues

17 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. Slide 17 PharmOut 2017

18 Local & Overall Penetration/Efficiency EN 1822 H 14 HEPA Challenge is set to MPPS 0.2 m Local pen < % Local pen < % Local pen < % Overall penetration < MPPS Slide 18 PharmOut 2017 No limit to number of local leaks, but Local & Overall Pen % must pass the limits. 18

19 Local & Overall In-situ Leak Test - H 14 HEPA 100% Upstream challenge (20-80 mg/litre PAO) PAO aerosol & photometer Local pen < 0.01 % Local pen < 0.01 % Local pen < 0.01 % Slide 19 PharmOut

20 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. Slide 20 PharmOut 2017

21 Filter leak testing options Revised ISO , 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. Slide 21 PharmOut 2017

22 Leak testing in-line filters Manual Photometer Facescan using an adapted bagout section. Automated face scan using particle counter system MPPS, rapid and minimal access intervention required. Courtesy Camfil-Farr Slide 22 PharmOut 2017

23 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 Slide 23 PharmOut 2017

24 And finally some BAS & CSV issues

25 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. Slide 25 PharmOut 2017

26 Thank you for your time. Questions? Gordon Farquharson Executive Consultant Slide 26 PharmOut 2017

27 PharmOut Copyright Notice All rights reserved This presentation and all associated materials are copyrighted and all rights reserved by PharmOut. No part of this presentation may be reproduced or transmitted in any form or for any purpose without the express permission of PharmOut in writing. The information contained herein may be changed without prior notice. Data contained in this presentation serves informational purposes only. PharmOut does not warrant the accuracy or completeness of the information, text, graphics, links, or other items contained within this presentation. This presentation is provided without a warranty of any kind, either express or implied, including but not limited to the implied warranties of merchantability, fitness for a particular purpose, or non-infringement. PharmOut shall have no liability for damages of any kind including without limitation direct, special, indirect, or consequential damages that may result from the use of this presentation. Slide 27 PharmOut 2017