MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS

1. MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS Module 5 Presented by : Deryck Smith Consulting Engineers

2. GMP Manufacturing Environments Air Handling Systems HVAC Systems Heating Ventilation Air Conditioning Module 5: Validation, Qualification & Maintenance

3. Validation / Qualification of HVAC Systems Topics for this Module: The definition and need for validation of HVAC Systems A qualification approach for HVAC Systems Retrospective qualification Inspection of HVAC Systems Maintenance of HVAC Systems 

4. Validation / Qualification of HVAC Systems Definition of Validation : The documented act of proving that any procedure, process, equipment, material, activity or system, actually leads to the expected results.

5. Validation / Qualification of HVAC Systems PIC/S Definition of Validation : Action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity or system actually leads to the expected results.

6. Validation or Qualification of a HVAC System ? Qualification : The action of proving that any equipment works correctly and actually leads to the expected results.

7. Validation or Qualification of a HVAC System ? • A system must be qualified to operate in a validated process • Equipment and systems are qualified • A process is validated • A number of systems make up a process 

8. Qualification / Validation Issues • A good design is essential, but it has to be complemented by: • Qualification of air handling systems • Process validation • Maintenance and periodic re-qualification • Adequate documentation

9. A Qualification approach for HVAC systems Key Definitions : • DQ - Design Qualification • IQ - Installation Qualification • OQ - Operational Qualification • PQ - Performance Qualification • VMP - Validation Master Plan • GEP - Good Engineering Practice 

10. A Qualification approach for HVAC Systems A Validation Master Plan User requirement document Design Qualification Installation Qualification Operational Qualification Performance Qualification

11. A Qualification approach for HVAC systems Qualification requires : Collaboration of experts Budget Planning 

12. A Qualification approach for HVAC systems • Planning : • Which systems are critical / non-critical ? (Risk assessment) • Direct or indirect impact (ISPE) • Which aspects of the system will be qualified ? • Which aspects of the system will be handled under GEP ? These decisions have implications on the extent, cost and time of the qualification process.

13. A Qualification approach for HVAC Systems Critical vs non-critical systems : (Risk or Impact assessment) • Impact assessment • Critical component • Non-critical component ISPE Definition: Impact assessment is the process by which the impact of a system on product quality is evaluated and the critical components within those systems are identified. 

14. Critical Components • A critical component within a system where the operation, contact, data, control, alarm or failure will have a direct impact on the quality of the product. • Eg. Supply air fan in an AHU, HEPA filters, HVAC control system. 

15. Non-critical Components • A non-critical component within a system where the operation, contact, data, control, alarm or failure will have an in-direct, or no impact on the quality of the product. • Eg. Main facility chiller, Eskom high tension transformer on site. 

16. A Qualification approach for HVAC Systems Model for “Direct Impact” systems PQ Test Plan Performance Qualification User Requirement (ie. What) OQ Test Plan (inc.FAT) Operational Qualification Functional Design (ie. How as schematic) Design Development IQ Test Plan (inc.PDI) Installation Qualification Detail Design (ie. How to make) Impact Assessment Implementation ISPE Baseline Guide Vol.5

17. A Qualification approach for HVAC Systems Model for “Indirect Impact” systems Commissioning Plan Performance Testing User Requirement (ie. What) (inc.FAT) Functional Design (ie. How as schematic) Setting-to-work & Testing Regulation & Adjustment Design Development (inc.PDI) Physical Completion & Inspection Detail Design (ie. How to make) Impact Assessment Implementation ISPE Baseline Guide Vol.5

18. A Qualification approach for HVAC Systems The Validation Master Plan • Validation policy • Organizational structure of validation activities • Summary of facilities, systems, equipment and processes to be validated • Documentation format to be used for protocols and reports • Planning and scheduling • Change control • References to existing documents  This document should contain : Ref : PIC/S Annex.15

19. A Qualification approach for HVAC Systems User requirement specification (URS) • What operational requirements are there ? • Required room temperatures and relative humidities • Cleanroom classifications for the areas • Single pass or re-circulated HVAC systems ? • Room pressures / Air flow directions • GMP requirements 

20. A Qualification approach for HVAC Systems DESIGN QUALIFICATION (DQ) • First step in the qualification of new HVAC systems. • It documents the design of the system and will include : • Functional Specification. • Technical / Performance specification for equipment. • Detailed Air Flow Schematics. • Detailed layout drawing of the system. 

21. A Qualification approach for HVAC Systems A thoroughly executed DQ process ensures the following : • Compliance with GMP’s and other regulatory requirements. • Design meets the user requirements. • Design details facility airflow and pressure cascade philosophy. • Design takes into account process and personnel flow (cross-contamination issues) • Design details materials of construction. • Design details safety requirements. • Full details of the intended construction prior to implementation. • Details all equipment that must be ordered.  ISPE Baseline Guide Vol.5

22. A Qualification approach for HVAC Systems Installation Qualification (IQ) • The goal of IQ is to verify and document the quality, installation and integrity of the HVAC system. • Execution of IQ protocols provides assurance that a HVAC system is installed in accordance with the qualified design. • IQ should highlight discrepancies between design layouts detailed in the DQ and what has been constructed (‘As-built” status) 

23. A Qualification approach for HVAC Systems IQ should include, but not be limited to the following : • Installation of equipment, piping, services and instrumentation checked against current engineering drawings and specifications • Collection and collation of supplier operating and working instructions and maintenance requirements • Calibration of measuring instruments requirements • Verification of materials of construction  Ref : PIC/S Annex.15

24. A Qualification approach for HVAC Systems Practical aspects of IQ : • Design drawings can be marked up and deviations highlighted. • DQ to be complete and signed off before IQ begins. • IQ protocols to be written and approved prior to implementation. • Check lists for components to be installed can be used. Items such as fans, fan motors, cooling and heating coils, filters, temperature and relative humidity sensors and differential pressure gauges can be included in check lists. • Duct and pipe pressure test reports. • Filter integrity tests. • Functionality Loop checks and alarm tests for HVAC control systems. 

25. A Qualification approach for HVAC Systems Practical aspects of IQ (cont.) : • Calibration of measuring instruments. • Calibration of additionally used instruments. • Initial cleaning records. • Basic commissioning checks. • Maintenance requirements. • IQ process checks that the correct components are installed in the correct location. • Materials of construction • Spare parts • Change controls 

26. A thoroughly executed IQ process ensures the following : • A fully verified installation that complies with the documented design. (all deviations will have been recorded and assessed.) • All equipment documentation and maintenance requirements would be documented. • Completed calibration of measuring instruments. • Materials of construction would have been verified. 

27. Operational Qualification (OQ) • The purpose of OQ is to verify and document that an HVAC system provides acceptable operational control under “at-rest” conditions. • ISPE definition : The purpose of OQ is to establish, through documented testing, that all critical components are capable of operating within established limits and tolerances. 

28. Operational control / operation within established limits and tolerances can be demonstrated by any of the following : • Ability to maintain temperature, relative humidity and pressure set points. • Ability to provide air of sufficient quality and quantity to ensure achievement of specified cleanroom conditions. • Ability to maintain any critical parameters stated in the DQ consistently. 

29. Operational Qualification should include, but not be limited to the following : • Tests that have been developed from knowledge of processes, systems and equipment. • Tests to include a condition or a set of conditions encompassing upper and lower operating limits, sometimes referred to as ‘worst case’ conditions.  Ref : PIC/S Annex.15

30. Practical aspects of OQ : • IQ reports must be completed and signed off. • OQ protocols to be written and approved prior to completion. • Measurement reports are required to demonstrate achievement of critical parameters as detailed in DQ. Eg: * Temperature measurement report * Humidity measurement report * Differential pressure measurement report * Air flow direction measurement report * Room particle count measurement report * All drawings etc. – done in ‘as-built’ status * All maintenance/ cleaning instructions available * All O & M staff to be trained to use and maintain the HVAC system. 

31. A Qualification approach for HVAC Systems PERFORMANCE QUALIFICATION ( PQ) • The purpose of PQ is to verify and document that an HVAC system provides acceptable operational control under ‘ full operational ‘ conditions. • PQ verifies that over time, the critical parameters , as defined in the DQ are being achieved. • PQ should follow successful completion of IQ and OQ. 

32. A Qualification approach for HVAC Systems PQ should include , but not be limited to the following:- • Tests, using production materials, qualified substitutes or simulated product, that have been developed from knowledge of the process and facilities, systems or equipment. • Test to include a condition or set of conditions encompassing upper and lower operating limits. 

33. A Qualification approach for HVAC Systems Practical aspects of PQ: • PQ is used to demonstrate consistent achievement of critical parameters over time. ( under manufacturing conditions) • PQ is ongoing. • PQ and OQ tests are sometimes performed in conjunction with one another. 

34. A Qualification approach for HVAC Systems Practical aspects of PQ (cont.) : • PQ tests can consist of the following :- • Air flow direction tests • Room pressure tests • Room temperature monitoring • Room relative humidity monitoring • Room particle monitoring • Microbiological monitoring 

35. Retrospective qualification • What happens when a detailed DQ, IQ and PQ process has not been performed ? • Evidence should be available (or prepared), to support and verify the operating parameters and limits for the critical variables of the operating equipment. Additionally, the calibration, cleaning, preventative maintenance, operating procedures and operator training procedures and records should be documented. ( PIC/S Annex 15) • Basically only OQ and PQ is carried out.

36. Inspection of HVAC Systems Inspector’s checklist for validation : Check that the manufacturer has : • A VMP and a multi-functional team for validation • A planned approach with defined requirements • Identified and described processes • An analysis of the amount of validation work to perform 

37. Inspection of HVAC Systems Inspector’s checklist for validation (cont.) : Check that the manufacturer has : • Selected methods & tools for validation • Created protocols for execution of the work • Performed DQ, IQ, OQ, PQ and documented the results • Exerted change control 

38. Inspection of HVAC Systems Inspector’s checklist for validation (cont.) : Check that the manufacturer has : • Authentic electronic records & signatures • Operating & Maintenance Manuals • “As-built” drawings of the ECS (HVAC System) • Schematic layout of the ECS (NB) • Maintenance schedules 

39. Maintenance of HVAC systems • The validation process should ensure that all maintenance information is obtained prior to the handover and use of the system. • The validation process should ensure that preventative and planned maintenance are put into practice. 

40. Maintenance of HVAC systems What happens when maintenance is done poorly or not at all ? • HVAC systems will not achieve the required critical parameters. • Correct air flows may not be guaranteed • Correct room temperature and relative humidities may not be achieved. • Room cleanliness can be compromised • Cross contamination could be promoted instead of being prevented. 

41. Validation, Qualification and Maintenance Summary • Qualification is a quality tool • A planned risk assessment based activity consisting of DQ, IQ, OQ and PQ. • Expensive and time consuming • Requires the manufacturer to assess which systems are critical and which are less critical. • Used to demonstrate that the systems are under control. 

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43. Questions & Answers Presenter contact details: Deryck Smith Consulting Engineers Inc, PO Box 39853, Faerie Glen, Pretoria, 0043 Tel 27 12 991-4010 Fax 27 12 991-7791 Cell 27 82 564-5330 E-mail: deryck@dsce.co.za Web site: www.dsce.co.za