Risk-Based Commissioning & Qualification Benchmarking

1. Risk-Based Commissioning & Qualification Benchmarking Educational Track #1

2. Agenda Part 1 (8:30 – 10:00) ISPE Baseline® Guide Volume 5: Commissioning & Qualification vs. ASTM E2500 – Mr. Robert Chew Overview of C&Q approaches – Abbott, Lilly, Pfizer Break – Vendor areas open (10:00 – 10:30) Part 2 (10:30 – Noon) Panel Q&A Wrap-up

3. ISPE Baseline Guide Volume 5: Commissioning and Qualification, vs. ASTM E2500 Robert E. Chew, PE President, Commissioning Agents, Inc.

4. My Background in Subject Official trainer for ISPE Baseline Commissioning and Qualification Guide Member of team that wrote ASTM E2500

5. Key Points to Compare Terminology Qualification practices Focusing the effort Roles and responsibilities Managing changes during the project

6. Terminology C&Q Baseline guide Commissioning Qualification ASTM E2500 Verification

7. Qualification Practices C&Q Baseline Guide “To meet the demands of the regulators” ASTM E2500 Not mentioned

8. Focusing the Effort C&Q Baseline Guide Impact assessments Direct impact systems and critical components V-model ASTM E2500 Risk assessment -> critical aspects

9. Roles and Responsibilities C&Q Baseline Guide Quality pre and post approves protocols; quality control role ASTM E2500 Quality involved in process requirements, risk assessments, critical aspects, and acceptance and release Subject matter experts used throughout

10. Managing Change C&Q Baseline Guide QA pre-approved change control implemented at start of IQ/OQ ASTM E2500 QA pre-approved change control implemented at start of manufacture of product for distribution

11. Common Elements Good engineering practices Planning Requirements definition Engineering design reviews Project change management Documented inspections and testing

12. Risk-Based Commissioning & Qualification Approach Abbott Laboratories Global Pharmaceutical Operations Steve Connelly

13. Overview Where Abbott Is Today C&Q Approach Commissioning & Qualification Activities How We Manage Cost Lessons Learned

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15. Commissioning & Qualification Approach C&Q Approach: Application of ISPE Baseline® Guide Volume 5: Commissioning & Qualification (last 2 years) Little to no implementation of ASTM E2500-07* Level 3 (Risk-based Maturity Model) Implementation: Corporate policies support Science & Quality Risk Management and includes Good Engineering Practice (GEP) reference Training ( RBA, GEP, ECM. Commissioning, Risk Assessments) Tools and Templates Discretion of the Validation Review Board (VRB)

17. Good Engineering Practices Formal acknowledgement of GEP in corporate policy Divisional GEP guideline consists of minimum requirements Additional divisional guidelines are in development for life-cycle management Calibration Maintenance Engineering change management Training to aid site support (implementation)

18. Requirements Based On Impact Category

19. Commissioning When supporting Qualification, Commissioning must include or address: Engineering Change Management (ECM) After point commissioning data intended to support Qualification

20. Qualification – Equipment User requirements Product and Process User Requirement (PURS) General User Requirements (GURS) Commissioning (in support of qualification) Test it once (or one set of multiple test repetitions, where appropriate); document it correctly Primarily installation activities, operational testing leveraged in some instances (VRB discretion);compile, summarize test results for VRB approval Qualification When approved, commissioning reports complete the IQ/OQ phase of Qualification with no additional “protocol” testing

21. Qualification – Software (APC/HMI/DCS) Categorization (based on product quality impact) Managing control issues for critical elements Supplier Assessments for direct impact systems only VRB discretion with technical advisory from Subject Matter Expert Holistic Approach Integrated Qualification document (IOQ for equipment/controls; as applicable) APC specific qualification requirements Traceability matrix = Design Qualifications (DQ) Commissioning = Qualification except critical items

22. Qualification – Facilities Indirect Impact Facilities - Commission Design and construction conforming to GEP Abbott Engineering Standards Direct Impact Facilities – Commission/Qualify Meet quality specifications (i.e. Aseptic facility, etc) Design and construction conforming to GEP Abbott Engineering Standards

23. Qualification – HVAC Categorization Interdependent with facility quality attributes For example: Continuous monitoring for critical environmental aspects; therefore facility and HVAC can be Indirect Impact (HVAC controls would then be qualified)

24. Qualification – Utilities Impact Categories - Typically critical or non-critical Utility systems typically not big source of Validation Change Request (VCR) sources Only regulatory requirement concern is typically Potable Water feed to purification Purpose of pretreatment usually to preserve life of purification equipment rather than direct impact of water quality

25. How We Manage Cost… In 2007, reviewed C&Q costs for several capital projects to: Establish a baseline Compare costs for the “traditional, validate everything” C&Q approach versus the risk-based C&Q approach Cost comparisons across projects difficult because Inconsistent reporting and project scope varies widely Drive cost reporting model for capital projects needed to: Address scope differences, track additional parameters: Number of Qualification Protocols per project Number of Qualified Systems Total Number of Systems Three parameters documented in C&Q Plan

26. Monthly Capital Project Status Reports are used to track costs and progress There is a wide variation in the tracking systems used by the engineers for the project costs Most project engineers / project managers use spreadsheets of their own design to track costs

27. Opportunities Identified for Consistent Reporting Engineering/Commissioning/Qualification costs categorized below Activities not linear, categorization to clarify “gray” areas of cost reporting Defines appropriate cost “bucket” for consistency across projects

29. Lessons Learned Risk-Based C&Q is an iterative process (one tiny step at a time) Corporate & divisional policies in place, tools developed, although success for various sites, concern about corporate & regulatory audits Sites want to maintain autonomy with guidance; common elements, not same approach (i.e. all engineers comply however variations due to specialty) Application: Site readiness tools - identifying opportunities for closing gaps

30. Lessons Learned Listen, Speak, Deliver. Communication is key. Quality may wonder: What if engineering doesn’t do its job?;ensure compliance Engineering may wonder: Quality = police & spell checkers; “right” the first tyme ? Application: Regular/frequent communication with VRB & project team

31. Lessons Learned Sustainable Paradigm Shift Sites: Implementation, accountability & ownership a must for sustainability Resources: People, time & money, site retaining technical knowledge Application: Training & support implementation as applicable

32. Thank you! Questions will be addressed during the Panel Q&A session (after break)

33. Eli Lilly & Company Commissioning and Qualification Approach

34. Eli Lilly & Company Approach to Commissioning & Qualification

35. Recent GFD C&Q Delivery Strategy ~ Baseline Guide approach (’02 – ‘07) Developed procedures governing C&Q activities Fully commissioned all assets ~ GEP Reserved qualification for critical aspects of DI systems only Leveraged commissioning documentation to support qualification – commissioning subject to GDPs Involved Quality at C&Q strategy level In addition, Simulation has been used to commission automation aspects CSV testing has been integrated within C&Q test documents

36. Fundamental C&Q Delivery Strategy ~ for Global Facilities Delivery (GFD) Capital Projects Commissioning & Qualification activities as they are required throughout the project delivery process C&Q activities occur throughout the entire process – timing and coordination are key SOPs define requirements for C&Q activities activities This diagram illustrates activity relationships to project phase and timing. Commissioning & Qualification activities as they are required throughout the project delivery process C&Q activities occur throughout the entire process – timing and coordination are key SOPs define requirements for C&Q activities activities This diagram illustrates activity relationships to project phase and timing.

37. This strategy has resulted in: Earlier resolution of issues Opportunity to understand systems Reduced Qualification time Reduced Qualification costs Fewer Qualification comments/discrepancies Supports risk-based approach by focusing qualification on product quality impact criteria Provides opportunity for issues to be resolved early in project cycle, prior to qualification Provides an opportunity for project personnel to operate and understand systems prior to qualification More rigorous checks during design, construction & commissioning results in faster qualification Results in more robust Qualification documentation All of these advantages contribute to budget and schedule efficienciesSupports risk-based approach by focusing qualification on product quality impact criteria Provides opportunity for issues to be resolved early in project cycle, prior to qualification Provides an opportunity for project personnel to operate and understand systems prior to qualification More rigorous checks during design, construction & commissioning results in faster qualification Results in more robust Qualification documentation All of these advantages contribute to budget and schedule efficiencies

38. C&Q Metrics

39. Typical C&Q Schedule Metrics ~ Durations Overall durations do not reflect the actual time required to complete tasks - Some executions were not performed as soon as they could have been, due to schedule and resource prioritization and/or equipment availability Duration averages include time to address discrepancies/change controls and to review/approve summary reports - the actual execution times are less We took an integrated approach to C&Q/CSV where CSV testing was included in FT, which led to longer FT durations Qualification averages include computer systems, which were not commissioned The durations are based on working days so it excludes weekends Overall durations do not reflect the actual time required to complete tasks - Some executions were not performed as soon as they could have been, due to schedule and resource prioritization and/or equipment availability Duration averages include time to address discrepancies/change controls and to review/approve summary reports - the actual execution times are less We took an integrated approach to C&Q/CSV where CSV testing was included in FT, which led to longer FT durations Qualification averages include computer systems, which were not commissioned The durations are based on working days so it excludes weekends

40. C&Q Cost Metrics ~ Historical view TIC – Total Installed CostTIC – Total Installed Cost

41. C&Q Budget Metrics  ~ capital projects completed in ‘07 Total Installed Cost C&Q Cost (% TIC) $319MM 6.0% $186MM 1.5% (comm. only) $180MM 5.5% $145MM 5.7% (incl. non-CQ activities) $14.5MM 4.3% $11.6MM 4.3% $7.2MM 2.2% Average: 4.7% (C&Q projects only) TIC – Total Installed CostTIC – Total Installed Cost

42. Lilly C&Q Work Breakdown Structure Lilly budgets/tracks C&Q expenses via 4 primary WBS categories: Planning & Design Commissioning Qualification Administration New C&Q Cost Data spec recently approved to provide guidance

43. Planning & Design - Subcategory C&Q plans and strategy Initial schedule development Estimating System classification Component classification System C&Q plans Vendor assessments User requirements Design review, spec review, drawing review reviews/tag list Engineering requirements Design Qualification Traceability Matrices

44. Commissioning - Subcategory FAT development FAT execution Receipt Verification development Receipt Verification execution Installation Verification development Installation Verification execution SAT development SAT execution Construction turnover packages

45. Qualification - Subcategory IQ development IQ execution OQ development OQ execution PQ development PQ execution

46. Administration - Subcategory Training Project management C&Q resource travel Administrative assistance Audits CSV support

47. Typical C&Q Budget Metrics  ~ Cost Breakdown (%)

48. C&Q Discrepancy Metrics ~ Philosophy C&Q delivery strategy based on risk mitigation approach DR/DQ reduced risk during Construction/Build, Commissioning, Qualification Construction quality assurance activities reduced Commissioning risks Simulation reduced risk during Commissioning (Startup, SAT, FT) Commissioning (RV, IV, FAT, SAT, FT) reduced risk during subsequent Commissioning activities and Qualification As risk decreased, the number of discrepancies also decreased - resulted in cleaner qualification documentation and better schedule adherence during qualification

49. Typical C&Q Discrepancy Metrics

50. Typical C&Q Discrepancy Metrics ~ Categories

51. User Requirements: Ensure URs are not too prescriptive and that they exclude design details Ensure URs are indeed requirements – if you aren’t sure or have to guess, then it’s probably not a true requirement Ensure URs are testable and applicable Ensure project profile is read and understood by all prior to developing URs Ensure experienced/right people are involved – typically Owner/User should drive Personnel Turnover: Ensure right people are assigned and committed to project Minimize turnover to avoid strategy changes/ learning curves Turnover changes may be improvements, but will still lose time analyzing strategies and/or adapting to new strategies/personnel Boundaries, System List, Strategies: Ensure cross functional input when determining system boundaries, system list, PLC configurations, and testing strategies Don’t use a single PLC to interface with multiple systems – difficult to determine boundaries, test, maintain Route all documents through a dedicated resource to ensure they are routed, reviewed, approved & controlled in a consistent manner Define what drawings are required, who is responsible for what, required formats, how they will be categorized and managed User Requirements: Ensure URs are not too prescriptive and that they exclude design details Ensure URs are indeed requirements – if you aren’t sure or have to guess, then it’s probably not a true requirement Ensure URs are testable and applicable Ensure project profile is read and understood by all prior to developing URs Ensure experienced/right people are involved – typically Owner/User should drive Personnel Turnover: Ensure right people are assigned and committed to project Minimize turnover to avoid strategy changes/ learning curves Turnover changes may be improvements, but will still lose time analyzing strategies and/or adapting to new strategies/personnel Boundaries, System List, Strategies: Ensure cross functional input when determining system boundaries, system list, PLC configurations, and testing strategies Don’t use a single PLC to interface with multiple systems – difficult to determine boundaries, test, maintain Route all documents through a dedicated resource to ensure they are routed, reviewed, approved & controlled in a consistent manner Define what drawings are required, who is responsible for what, required formats, how they will be categorized and managed

52. Current GFD C&Q Delivery Strategy ~ Enhanced Baseline Guide approach (last 2 years) Conducted several six sigma initiatives to improve C&Q processes Developed additional procedures and best practices pertaining to C&Q GDP SOP Change Management SOP Transfer of Care, Custody and Control SOP Discrepancy Management Best Practice Developed new specifications governing the following Vendor data and documentation FAT/SAT C&Q cost data Defined new project information management role Implementing new requirements definition process based on systems engineering principles Implementing formal Construction QA program An ISPE Task Team has been formed in an attempt to standardize on vendor data and documentation requirements An ISPE Task Team has been formed in an attempt to standardize on vendor data and documentation requirements

53. Current GFD C&Q Delivery Strategy ~ Enhanced Baseline Guide approach (cont.) Developed Automation Lifecycle Management engineering standard to accommodate integration of CSV and C&Q resulting in: Elimination of duplicate requirements, design reviews, testing Elimination of “all or nothing” approach to software testing Allowance for risk-based delivery strategies Leverage offline or simulation testing to meet requirements Assessing risk in areas beyond product quality to streamline C&Q delivery Vendor risk Technology risk Automation strategy Leveraging vendor testing to support commissioning vs. just using as contractual gate/risk mitigation An ISPE Task Team has been formed in an attempt to standardize on vendor data and documentation requirements An ISPE Task Team has been formed in an attempt to standardize on vendor data and documentation requirements

54. Questions? Q&A

55. Risk Based Commissioning & Qualification Benchmarking Presented by: Nick Andreopoulos Senior Manager/Team leader Pfizer Global Engineering Peapack, NJ Chris Beltz Senior Manager/Team Leader Pfizer Quality Operations Kalamazoo, MI

56. Agenda Basis of C&Q Practices C&Q Program Management Approach C&Q Cost Management Key Lessons

57. Current C&Q Practices Primarily based on C&Q Baseline® Guide 5 Certain sites have streamlined C&Q process C&Q “Lite” version for small projects and minor equipment changes Leveraging of Commissioning tests into IOQ Applying some ASTM concepts – Focusing IOQ on risk to product quality/patient safety Functional Level Impact Assessment - Replacing Component Level Impact Assessment Currently developing and piloting full ASTM E2500 based Verification approach at targeted sites

58. C&Q Program Management C&Q supported jointly by Quality, Engineering and Automation/IT Quality requirements defined in Corporate Quality Standards C&Q Approach defined in Global Practices Sites develop their own procedures and validation master plans based on the global documents

59. C&Q Cost Management C&Q costs that are associated with equipment qualification are included in Project Capital budgets. Process Validation and Cleaning Validation are not included in project budgets C&Q cost managed by Project team

60. Key C&Q Lessons Learned Upfront involvement by key stakeholders in the Assessment steps to define the appropriate scope for qualification IOQ scope should be focused on critical aspects/functions. All other testing is GEP Testing documents should be based on SME execution and leveraged, where possible, from vendors. Level of documentation should be commensurate with risk to product quality/patient safety. Roles/Responsibilities need to be clearly defined at the outset of projects

61. Risk-Based Commissioning & Qualification Benchmarking Educational Track #1 Part 2

62. Agenda Part 1 (8:30 – 10:00) ISPE Baseline® Guide Volume 5: Commissioning & Qualification vs. ASTM E2500 – Mr. Robert Chew Overview of C&Q approaches – Abbott, Lilly, Pfizer Break – Vendor areas open (10:00 – 10:30) Part 2 (10:30 – Noon) Panel Q&A Wrap-up

63. Thank You!! Robert Chew, Commissioning Agents Matt Warhover, Commissioning Agents Steve Connelly, Abbott Laboratories Dave Dolgin, Abbott Laboratories Scott Hamm, Eli Lilly Rick Gunyon, Eli Lilly Nick Andreopoulos, Pfizer Chris Beltz, Pfizer Great Lakes Chapter Board and Directors Ron Dunn, GLC Manager