Risk-Based Validation The Benefits of the GAMP Approach

Transcription

1 Risk-Based Validation The Benefits of the GAMP Approach Kevin C. Martin Chair, GAMP Americas Sr. Vice President Azzur Group LLC

2 Agenda 20 Years of the GAMP Organization GAMP Benefits GAMP Contribution Validation Productivity Lean Validation Current Technology Trends Current Regulatory Activity 2

3 20 years of GAMP Development Validation Productivity! plus 3

4 4

5 GAMP Americas Leadership Officers Chairman: Kevin Martin, Azzur Group Co-Chairman: Michael Rutherford, Eli Lilly Secretary: Lorrie Schuessler, GSK ISPE Staff PM Scott Ludlum Steering Committee Winnie Cappucci*, Retired- Bayer Waunetka Clark, Abbott Jim John, ProPharma Group Paige Kane, Pfizer Klaus Krause, Allergan Eugene Longo, GAMP Puerto Rico Randy Perez, Novartis Judy Samardelis, Medimmune Eric Staib, Covance Robert Tollefsen, FDA Bob Wherry, Sunovion Blue indicates GAMP Council *Denotes GAMP Council Chair 5

6 Active GAMP SIGs GAMP Americas Laboratory Systems Manufacturing Execution Systems (co-chaired with Europe) Risk Management Joint Equipment Transition Team (JETT) R&D / Clinical Systems (coordinated with Europe) Automated Testing (sub-set of Testing SIG) Outsourcing and Offshoring (with Europe) IT Infrastructure Control & Compliance (with Europe) Metrics GAMP Europe Process Control Systems Testing (with USA) Supplier Relationships Outsourcing and Offshoring (with USA) Calibration GxP Controls Framework (proposed) GAMP D-A-CH Supplier Cooperation Open Source Software Development Models and Methods GAMP Italia Equipment Qualification Workgroup GAMP Nordic Virtualization 6

7 Active GAMP SIGs - Brazil GTG "Validation of IT Infrastructure and Processes GTG " Validation of PLCs, Automated Systems, Shop-floor Systems, MES and BMS GTG "Change Management for Computerized Systems and Maintenance of Validated Status : GTG Understanding e-records and e-signatures (ANVISA / EMA Annex 11 / 21CFR Part 11 / GAMP) GTG Validation Master Plan and Validation Plan for CSV GTG Legacy Systems GTG " Qualification and Suppliers Assessment GTG "Testing GxP Systems (base GPG GAMP) GTG "Organizational Structure for CSV 7

8 GAMP Good Practice Guides 1. Validation of Process Controls Systems (Second Edition Feb 2011) 2. Calibration Management (Second Edition Nov 2010) 3. Manufacturing Execution Systems A Strategic and Program Management Approach (Feb 2010) 4. A Risk-Based Approach to Operation of GxP Computerized Systems - A Companion Volume to GAMP 5 (Jan 2010) 5. Electronic Data Archiving (Jul 2007) 6. Testing of GxP Systems (Dec 2005)* (2 nd Edition 3Q2012) 7. Global Information Systems Control and Compliance (Nov 2005) 8. IT Infrastructure Control and Compliance (Sep 2005) 9. Validation of Laboratory Computerized Systems (Apr 2005) (2 nd Edition 2Q2012) 10. Risk-Based Approach to Electronic Records and Signatures (Feb 2005) 11. Legacy Systems (Nov/ Dec 2003)* * Available as a download at no cost to ISPE Members Only 8

9 GAMP 5 GAMP 5 Overview Published: Feb

10 GAMP 5 Continues to Address Current regulatory initiatives FDA s cgmps for the 21 st Century PIC/S Guidance Risk-based Part 11 Guidance Global Standards ICH Q8, Q9, Q10 ASTM E2500 Escalating cost pressures mandate efficiency Facilitate a single company QMS Need to take full advantage of supplier capability Better compliance with less cost! 10

11 GAMP 5 Simplified V-model This Validation model better illustrates scalability Verifies options for phases Plan Blended specifications (e.g. Validation URS/FS, Activities FS/DS, even URS/FS/DS) Design review as opposed to formal DQ Blending User of classical qualification Verifies (e.g. IOQ, OQ/PQ, melding Acceptance of Requirements computer validation with equipment C&Q) Development Activities (URS) Plan Functional Specification (FS) Design Specify Specification (DS) GAMP 5 stresses that this model does not imply a System waterfall Build development methodology Activities Verifies Risk Management throughout the process Verifies Build or Configure System Build (including developer tests) Developer tests (Structural, unit, & integration) Verify Installation (IQ) Report Functional testing (OQ) testing (PQ) Validation Report Verification Activities This can be applied to nonlinear approaches like spiral or iterative methodologies, agile software development, etc. 11

12 GAMP 5 Life Cycle Concept URS GxP Assessment Repetitive V Activities Within the Life Cycle Release Changes migration Concept Project Operation Retirement Supplier Involvement* * This could be a complex supply chain Supplier may provide knowledge, experience, documentation & services throughout lifecycle Features: Simplified V- Model Plan Specify Build Verify Report Risk mgmt throughout process Repetition of V- activities for changes Incorporates end-of-life activities 12

13 Risk Management Goals Systematic process for identifying, assessing, mitigating, controlling, and communicating risk, based on Good science Process and product understanding Recognize that zero risk is impractical and unattainable Aim is for acceptable risk Consistent with risk-based approach based on ISO (and ERES GPG) as well as other contemporary risk based tools 13

14 5-Step Quality Risk Management Process Step 1 Perform initial risk assessment & determine system impact Step 2 Identify functions impacting patient safety, quality, and data integrity Step 3 Perform functional risk assessments & identify controls Step 4 Implement & verify appropriate controls Step 5 Review Risks and monitor controls 14

15 Focus Validation Effort Focus Validation Effort The Desired State Historical State 1990 s Validation Approach Desired State Risk Based Approach High Medium Low High Medium Low 15

16 Stakeholders the GAMP Benefits All stakeholders depend on reliable systems Performing as expected from the beginning continuously with minimal attention A proven roadmap when going from manual to automated systems We have a great responsibility! 16

17 GAMP 5 Enables Increased Validation Productivity Focussed on efficient and effective validation Making validation productive OED: producing abundantly Webster's: Yielding results, benefit or profit Eliminate the Waste!!! 17

18 Universal Approach GAMP methodology applies to all types of systems Large database systems Process control systems Spreadsheets etc. Needs tailoring to each project for maximum efficiency Consider all the elements of the validation process 18

19 Uniform Approach The V model is almost universally applicable It is capable of considerable flexibility Many dialects exist Fundamentals remain Design Review Plan >Check > Do > Record Document Handover Planning Specifications Protocols Change management 19

20 QMS* for Systems Validation The Validation Process is well-documented Based on QMS principles Widely understood Adopts standard elements of QMS Planning Specifications Risk-based approach Verification Documentation Change management Continuous improvement *QMS = Quality Management System 20

21 Knowledge of Systems To validate effectively we need to know our systems; Why we want them What they do How they do it Where the risks lie How the risks are controlled Follow a System Life Cycle - Use GAMP5 as a tool Payback is immediate increased efficiency of operation 21

22 Benchmarking for Continuous Improvement Policies and Procedures 12 Good Validation Practices Good Project Management Practices Validation Planning Validation Strategy Specifications and Design Review Protocols Acknowledgment: David Selby, NSF-DBA Documentation Change Management Practices Training Handover Maintaining Control in Operation Post-project reviews 22

23 Benchmark Assessment Highest scores highlighted Green Next lowest highlighted Yellow Lowest Scores highlighted Red Absolute numbers not meaningful Averages are more reliable Look at the concentration of colour Acknowledgment: David Selby, NSF-DBA 23

24 Benchmarking Results - Typical Policies and Procedures Protocols, Documentation Change Management Handover Control in Operation Post-project Reviews Project Management Planning Strategy Specifications and Design Review Training Acknowledgment: David Selby, NSF-DBA

25 Example 1: Ampoule Filling Line Mid 90s Comparison of validation of two liquid injection filling lines Specification Development Pre-GAMP Protocol Development FAT Testing 5 days 1 week 3 days Initial efficiency 35% Final Efficiency 65% Specification Development Post-GAMP2 Protocol Development FAT Testing 5 weeks 4 weeks 2 weeks Initial efficiency 75% Final Efficiency 95% 25

26 Cost Effective Approach How much does Validation Cost? Some figures (% of total project cost): Current industry average 20 25% Major pharma company (top 10) 16% GSK 4%* Pfizer 4%* Best in class ~ 1.2% * Figures published in

27 Example 2: SAP Financials GAMP methodology applied to global implementation of SAP Financials Scenario: Lead site Decision to use validation rigor (GAMP Methodology) for all modules Lead by QA validation expert Tough to get Finance to understand what that meant IT Project manager: This guy has no idea how to implement a finance system. Testing went like a dream! Project on time and on budget We ve never had a test phase that went so smoothly with so few problems Acknowledgment: Randy Perez, Novartis 27

28 Example 3: Re-engineering the Verification Process Validation Waste Transportation Waiting Motion Defects Inactive players High training requirement Physical document circulation Long lead times for meetings Slow project initiation Priority conflicts Implementation of optional features Unclear purpose Acknowledgment: Guy Wingate, GSK Over-production Wrong skills mix Sequential activities Multiple forms Too many signatures Extra Processing Staff turnover Multiple planners Late detection Effort to re-work Too many documents Too many people Inventory WASTE 28

29 Example 3: Re-engineering the Verification Process Savings identified: Adopting good practices ~5% Adopting standardized practices ~30+% Focussing of GMP activities ~20% Scaled approach ~10% Leverage supplier expertise Rigorously applied risk-based approach Average Cost of Validation Acknowledgment: Guy Wingate, GSK 29

30 Example 3: Re-engineering the Validation Process Upgrade Projects Cost Savings* 1 50% 2 58% 3 72% Total Savings >$1.5m Cost savings comparing V model alone (GAMP 4) vs. V model + E 2500 (GAMP 5) Acknowledgment: Lily Mo, Pfizer Global Quality Operations 30

31 Example 4: Application of Risk Management (Scaleability) High Medium Low Definition Severe potential harm to patients, (e.g. death, hospitalization, long term effects). Risk has potential for nonserious impact on patient safety and/or product quality. Risk has little or no potential impact on patient safety and/or product quality. Criteria Product is unusable or ineffective such that harm is likely. Loss or corruption of records has potential for severe harm to patients....and so on for your organisation. Impacts product quality but with no or negligible impact on patient safety (e.g. cosmetic defect). Loss or corruption of records would have non-serious impact on patient safety or product quality.... and so on for your organisation....think carefully here... Regulatory requirement with little or no impact on product quality and/or patient safety. Loss or corruption of records would violate regulatory requirements but have no impact on patient safety or product quality...and so on for your organisation. Possible Examples Training management for staff operating in aseptic area. Dispensing of active ingredients for production, sterilization hold times. Incomplete break line on OTC tablet. Checkweigher detection of incompletely filled blister packs. Training management for nonproduction staff. Corrupt electronic signature on audit report. Acknowledgment: Ellis Daw, GSK 31

32 Example 4: Application of Risk Management (Scaleability) Probability of Failure (Development Classification) Severity 1 (Customised) 2 (Configurable) 3 (Non-Configurable) High (H) Intensive Standard Minimal Medium (M) Intensive Standard Minimal Low (L) Standard Minimal Minimal Rigor of Verification Intensive Standard Minimal Positive and negative testing (as appropriate) -evidence required (e.g., critical screen shots, report(s), witness signatures - QA and 2 nd person review required Positive testing, including multiple/alternative path testing -standard evidence required (outcome, tester initials, date) - 2 nd person review required (QA review not required) Minimal testing -Vendor or leveraged documentation - verification may be required to test requirement - 2 nd person review required (QA review not required) High: functions impacting product release, process control, batch records, complaints, recall, regulatory filings, adverse event recording etc. Medium: functions impacting support processes driven by GMP regulations, critical business processes Low: functions impacting supporting processes NOT driven by regulation Acknowledgment: Lily Mo, Pfizer Global Quality Operations 32

33 Example 5: Leveraging Supplier Testing System Business Workflow Mapping Tool Limited configuration required to implement at customer s site Approach Extended audit to verify Supplier Functional Risk Assessment and Testing Additional effort, 4 days to conduct the review of Functional Risk Assessment and Supplier Testing Outcome Regulated company testing more spot checks of high impact functions (3 days) Original regulated company test plan allowed for 6 man weeks testing Acknowledgment: Chris Reid, Integrity Solutions Ltd. 33

34 Example 6: Business Benefits Pre GAMP Business processes not defined Requirements unclear/incomplete Projects over-ran User expectations not met Post GAMP Adoption of lifecycle approach Brought discipline (painfully!) Users understood business processes Users understood business needs Requirements and quality attributes traceable to business process Requirements prioritised Compliance to timelines and costs (mostly) System understood by users Systems accepted by users Traceability made maintenance easy Acknowledgment: Winnie Cappucci (formerly Bayer) 34

35 What is Lean Validation? Lean Validation is defined as the delivery of validation services with as little waste as possible. 35

36 History of the Problem 36

37 Problem Statement COST OF VALIDATION ~ 25% of the total capital TIME Inadequate cycle times Effort takes too long Inability to support timelines based on business needs 37

38 What have we typically seen? No uniform practice Unclear expectations Unclear roles and responsibilities Duplication of effort and rework Significant resource commitment Inconsistencies Functionally siloed activities Re-interpretation of requirements leading to re-drafting of protocols Multiple reviews / approvals for each protocol 38

39 What is the impact? Major cause of contract breaks schedule cost Work environment stress anxiety morale 39

40 Current Qualification Practice IQ rework churn OQ PQ rework 40

41 Let s Re-design the Process Integration and alignment of Qualification & Capital execution Application of Front-End Loading (FEL) principles Early cross-functional involvement, understanding, consensus and commitment Conformance to regulatory and cgmp expectations from the start 41

42 Re-design Tools Defined, integrated work flow process Identification of key milestones identified interdependencies between construction & qualification activities Responsibilities Matrix Defined roles and responsibilities Standard Qualification templates Process & Packaging Equipment Laboratory Systems Any Automation!!! 42

43 Cost Savings Reduced cost to less than 20% of capital expenses Achieved a cost profile of 10% or less of capital expenses Eliminating or reducing non-value added work 43

44 Some Other Cost Savings Measures 44

45 Document Approvers Typical approval cycle is five validation documents approvers Lean Approach: Should be two document approvers System Owner Quality 45

46 Benefits (of reduced approvers) Reduced cycle times Faster turnaround of verification documents Cost efficient Reduced numbers of EDM users Lower license cost for reduced number of document approvers 46

47 Verification Forms Implementation of verification forms instead of protocols Driven by SOP Individual Forms are pre-approved Installation & Functional Verification forms Forms can be created by leveraging existing protocols 47

48 Verification Forms (cont.) Forms can be created from requirements and design documents Forms can be used for the validation of changes to existing systems Examples of verification forms Security verification Recipe verification Audit trail verification Parameter verification P&ID verification Loop check verification 48

49 Benefits of implementing verification forms Cycle time reduction Faster turnaround time Only one approval cycle Cost reduction: ~ $ 750 per form vs $ 5,000 per protocol 49

50 Productive Validation its Very Important! Companies need systems for: operations to make much-needed products for patients And to promote: increased assurance of product quality sustainability Systems need validation Validation needs to be efficient and effective by: having an efficient validation process applying effective governance good in-depth training and expertise continuous improvement 50

51 So what is left to do? Improve our validation processes they re capable of much further refinement Standardize the approach Judiciously apply risk management and E 2500 Spend project time on the front end of the system life cycle process Look at the final steps around handover Get into the continuous improvement mind-set 51

52 Validation Productivity Priorities Upgrade the validation system Focus on the the front end (validation planning, strategy and specification development) the back end (handover and maintaining control in operation)

53 Validation Productivity Priorities Standardize the approach across the organization Focus on Defining the deliverables Scalability Integration of E 2500 into the process Involvement of SMEs and QA Applying Globally 53

54 Validation Productivity Priorities Focus on Integrating risk management into the entire process Apply it ruthlessly Spread it throughout the organization once it s right High Medium Low 54

55 Validation Productivity Priorities Spend project time on planning using risk management using the expertise of SMEs on design review 55

56 Validation Productivity Priorities and don t forget Handover data accessibility for users knowledge transfer measured performance criteria 56

57 Validation Productivity Priorities Continuous Improvement Embrace new approaches Learn from each project Build the learning back into the validation process Spread the word 57

58 Validation Productivity The target? Continuous improvement cost effective validation projects a few % of project cost from be part of the solution 58

59 Thank You! Resources / More Information Kevin C. Martin GAMP Americas Chair Azzur Group LLC Sr. Vice President kevin.martin@azzurgroup.com Michael L. Rutherford GAMP Americas Vice Chair Consultant Business Systems Support Development Center of Excellence Eli Lilly and Company ml.rutherford@lilly.com ISPE GAMP Community of Practice (COP) Website 59