1. www.methoda.com MethodGXP The Solution for the Confusion

2. Methoda Computers Ltd 2 Company’s Background  20 years specializing in Quality Assurance, Software Engineering and IT Management  10 years specializing in Software Validation  60 Senior Consultants (at least 10Y experience)  Leading methodology and knowledgebase for software engineering and IT management  Quality certification for ISO-9001  Proven methodology for the FDA regulations

3. Methoda Computers Ltd 3 The Challenges  Complexness to achieve qualitative product and processes  The need to be compliant with different standards and regulations (CE, FDA, ISO, etc)  Many guides for similar and complementary requirements  Much confusion and unclear instructions  Potential for duplication in documents, processes and activities

4. Methoda Computers Ltd 4 Too many Guides Design Control Guidance 21 CFR Part 11 General Principle of SW Validation OTS Software GeneralPrinciples of Process Validation General Principles of Process Validation ISO 9000 ISO 13485 Pre-market Submissions GAMP 4 cGMP-QSR

5. Methoda Computers Ltd 5 Main Requirements  "Any software used to automate any part of the device production process or any part of the quality system must be validated for its intended use..“  "Software validation activities may occur both during, as well as at the end of the software development life cycle to ensure that all requirements have been fulfilled."  "A conclusion that software is validated is highly dependent upon comprehensive software testing, inspections, analyses, and other verification tasks performed at each stage...“  “Establish DOCUMENTED EVIDENCE that provides a HIGH DEGREE of assurance that a computer system or software will CONSISTENTLY perform within its predetermined specifications and quality attributes.”

6. Methoda Computers Ltd 6 21 CFR Part 11- More requirements and challenges  “.. computer systems used to create, modify, and maintain electronic records and to manage electronic signatures are also subject to the validation requirements.“  “… FDA will consider electronic records to be equivalent to paper records, and electronic signatures equivalent to traditional handwritten signatures.”  Ensure the authenticity, integrity, and, when appropriate, the confidentiality of electronic records.... ensure that the signer cannot readily repudiate the signed record as not genuine.”

7. Methoda Computers Ltd 7 Summary of Challenges  Overload of information and instructions  Compliance with the regulations is essential  Advanced methodology is required for reduced risks and business efficiency Pragmatic solution is required!

8. Methoda Computers Ltd 8 Pragmatic solution - A risk based approach  GAMP IV A risk based approach will be acceptable, but how do you legally justify your risk assessment?  “General Principles of Software Validation, Draft Guidance Version 1.1” “…The resultant software validation process should be commensurate with risk associated with system, device or process”

9. Methoda Computers Ltd 9 Pragmatic solution - A risk based approach  Pre-Market: “..risk estimation for software products should be based on the severity of the hazard resulting from failure...”  GPOSV: "The magnitude of software validation effort should be commensurate with the risk associated with the device….“  GAMP 4: The categories are based on the increasing risk of system failure with the progression from standard SW and HR to custom…”

10. Methoda Computers Ltd 10 Methoda’s Risk Based Approach Pragmatic Solution Policy Risk Based Approach Severity & Category Validation Efforts Part 11 Priorities & Efforts

11. Methoda Computers Ltd 11 Methoda’s Risk Based Approach  Risk will be determined by assessing:  The Level of Concern to determine the level of the validation activities  The complexity/category of the system to determine the validation deliverables

12. Methoda Computers Ltd 12 Criteria for the Appropriate Solution  Business efficiency - Quality product and development process  Receiving the right information (and terminology) to support submissions  Integration of all regulatory requirements  Elimination of duplication- globally aligned system eliminates unique local requirements  Cost effective solution

13. Methoda Computers Ltd 13 MethodGxP - The Solution  Tool-Kit that is ready for implementation  Single Standard Quality System that complies with the QSR, ISO, and CE Mark  Comprehensive procedural framework  Solution life cycle supports good engineering practice  Policy that supports compliance with requirements and regulations

14. Methoda Computers Ltd 14 MethodGxP - The Solution  Comprehensive Risk Management process to minimize the requirements  Efficiency and NO duplications DO IT RIGHT the FIRST TIME

15. Methoda Computers Ltd 15 Validation Tasks  System Mapping  Gap Analysis  Policy  Work Plan for closing the gaps  Validation Deliverables: VP, IQ, OQ, PQ, TM, VSR and vendor documented evidences  Maintenance of system  Periodic Review

16. Methoda Computers Ltd 16 Validation Life Cycle User Requirements Functional Specifications Design Qualification Performance Qualification Operational Qualification Installation Qualification Installation System Validation Plan Validation Summary Report

17. Methoda Computers Ltd 17 Example of GXP Validation Folder

18. Methoda Computers Ltd 18 Example of Templates  Gap Analysis Gap Analysis  Systems Validation Policy Systems Validation Policy  Computerized System Validation Program (CSVP) Computerized System Validation Program (CSVP)  Installation Qualification (IQ) Installation Qualification (IQ)  Operational Qualification (OQ) Operational Qualification (OQ)  Performance Qualification (PQ) Performance Qualification (PQ)  User Requirements Specification (URS) User Requirements Specification (URS)  Traceability Matrix (TM) Traceability Matrix (TM)  Validation Summary Report (VSR) Validation Summary Report (VSR)

19. Methoda Computers Ltd 19 Acceptable Evidence  Documented evidence for Quality System in the development process  Documented evidence for good engineering practice (Specifications, designs, reviews, testing, etc)  For critical systems, a vendor audit may be required

20. Methoda Computers Ltd 20 Process Recap - MethodGxP Advantages  Cost effective solution  Simple and efficient model  Single Checklist  Easy to understand - easy to use  Compliant with the regulations  Comprehensive solution from concept to maintenance

21. Methoda Computers Ltd 21 Process Recap - MethodGxP Advantages  A proper Implementation of MethodGxP results in:  Improved system quality  Meeting Goals, Schedule and Budget  Improving Cost/Performance  Control & Management  Satisfied User

22. Methoda Computers Ltd 22 GxP Implementation Plan for the pharmaceutical market Activity Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

23. Methoda Computers Ltd 23 Phase 1 - Gap Analysis  Determining the actions needed to bring the system into compliance with established software validation and 21 CFR Part 11 regulations  Input: Regulation requirements and systems’ gaps  Output: Action items to close the gaps – Gap analysis template Gap analysis template Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

24. Methoda Computers Ltd 24 Phase 2 - Policy  Based on Risk Based Approach  Specifies all validation activities for all regulated computer systems  Input: FDA requirements, good engineering practice  Output: Policy documentPolicy document Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

25. Methoda Computers Ltd 25 Phase 3 - Work Plan  Detailed action items for each system with priorities and required recourses  Input: Gap analysis and Policy  Output: Work plan Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

26. Methoda Computers Ltd 26  Deliverables and Activities:  Validation Plan Validation Plan  User Requirements Specification User Requirements Specification  Installation Qualification Installation Qualification  Operational Qualification Operational Qualification  Performance Qualification Performance Qualification  Testing Execution  Traceability Matrix Traceability Matrix  Validation Summary Report Validation Summary Report  Input: Policy  Output: Validated systems Phase 4 - Validation Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

27. Methoda Computers Ltd 27 Phase 5 - Training  To ensure reliable system operation  To ensure reliable procedures operation  Input: User guide, SOPs  Output: Trained users GAP Analysis Policy Work Plan Validation Training Software Validation maintenance Periodic review System retirement

28. Methoda Computers Ltd 28 Phase 6 - Software Validation Maintenance  Any change to equipment and computer systems that may affect the system’s validation status should follow documented procedures and should be formally approved  Input: Changes  Output: Validated systems Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

29. Methoda Computers Ltd 29 Phase 7 - Periodic Review  Periodic reviews will be performed and documented for each validated system to ensure its validation status is still current  Input: System status  Output: Validated systems Gap analysis Policy Work plan Validation Training Software Validation maintenance Periodic review System retirement

30. Methoda Computers Ltd 30 Step 8 - System Retirement  Disposition of system software  Disposition of system documentation  Migration (if necessary) or archiving of data  Input: Retired System  Output: Historical data that can be retrieved Gap analysis Policy Work Plan Validation Training Software Validation maintenance Periodic review System retirement

31. Methoda Computers Ltd 31 www.methoda.com