1. Module 4 | Slide 1 of 28 January 2006 Qualification and Validation Basic Principles of GMP Section 4

2. Module 4 | Slide 2 of 28 January 2006 Qualification and Validation Objectives lTo review basic aspects of qualification and validation lTo understand the scope of qualification and validation lIntroduction to documentation associated with validation (See also Supplementary Training Module on Validation)

3. Module 4 | Slide 3 of 28 January 2006 Qualification and Validation Definitions Validation lAction of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results Qualification Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results ( Validation usually incorporates the concept of qualification) Glossary

4. Module 4 | Slide 4 of 28 January 2006 Qualification and Validation Principle lEssential part of GMP lManufacturer to identify what qualification and validation work is required lProve that critical aspects of work are controlled lKey elements of qualification and validation defined and documented 4.1, 4.2, 4.8

5. Module 4 | Slide 5 of 28 January 2006 Qualification and Validation Scope lDocumented evidence to prove that, e.g. äPremises äSupporting utilities äEquipment have been designed in accordance with GMP lAlso referred to as Design Qualification (DQ) where appropriate 4.3(a)

6. Module 4 | Slide 6 of 28 January 2006 Qualification and Validation Scope lDocumented evidence to prove that, e.g. äPremises äSupporting utilities äEquipment have been built and installed in accordance with their design specifications lAlso referred to as Installation Qualification (IQ) 4.3(b)

7. Module 4 | Slide 7 of 28 January 2006 Qualification and Validation Scope lDocumented evidence to prove that, e.g. äSupporting utilities äEquipment operate in accordance with their design specifications lAlso referred to as Operational Qualification (OQ) 4.3(c)

8. Module 4 | Slide 8 of 28 January 2006 Qualification and Validation Scope lDocumented evidence to prove that, e.g. äSupporting utilities äEquipment perform consistently in accordance with their design specifications – see also next slide on PV lAlso referred to as Performance Qualification (OQ) 4.3(d)

9. Module 4 | Slide 9 of 28 January 2006 Qualification and Validation Scope lDocumented evidence to prove that: äA specific process will consistently produce a product meeting its predetermined specifications and quality attributes lAlso referred to as Process Validation (PV) 4.3(d)

10. Module 4 | Slide 10 of 28 January 2006 Qualification and Validation Scope Qualification and validation: lApplicable to any aspect of operation which may affect the quality of the product äDirectly or indirectly lIncludes premises, facilities (utilities), equipment, processes lIncludes significant changes 4.4

11. Module 4 | Slide 11 of 28 January 2006 Qualification and Validation Principle lQualification and validation should be done in accordance with an ongoing programme äInitial qualification and validation äAnnual review lMaintain continued validation status lPolicy described in relevant documentation, e.g. quality manual, or Validation Master Plan 4.5, 4.6

12. Module 4 | Slide 12 of 28 January 2006 Qualification and Validation Types of Documentation lValidation Master Plan (VMP) lValidation protocols lValidation reports lStandard Operating Procedures (SOPs)

13. Module 4 | Slide 13 of 28 January 2006 Qualification and Validation Documentation lClearly defines responsibility of performing validation lConducted in accordance with predefined, approved validation protocols lRecorded results and conclusions presented in written validation reports – prepared and stored lProcesses and procedures should be established on the basis of these results 4.7 – 4.10

14. Module 4 | Slide 14 of 28 January 2006 Qualification and Validation Importance: lPremises, utilities, equipment and processes lCritical importance and particular attention paid to validation of: äAnalytical test methods äAutomated systems äCleaning procedures 4.11

15. Module 4 | Slide 15 of 28 January 2006 Basic Principles of GMP What are the qualification and validation requirements here for this piece of equipment, as well as the step in production?

16. Module 4 | Slide 16 of 28 January 2006 Annex 6 Qualification and Validation WHO References lGood manufacturing practices (GMP): guidelines on the validation of manufacturing processes lValidation of analytical procedures used in the examination of pharmaceutical materials

17. Module 4 | Slide 17 of 28 January 2006 Qualification and Validation Example of priorities for process validation Type of process Requirement lNew Every new process before approval for routine lExisting: äSterile products All processes affecting the sterility, and manufacturing environment including sterilization stage äNon-sterile Low dose tablets and capsules: mixing and granulation; content uniformity (and other parameters) Other tablets and capsules: uniformity of mass (and other parameters)

18. Module 4 | Slide 18 of 28 January 2006 Qualification and Validation lThe Validation Master Plan may contain elements (and policy) such as: äApproval page and table of contents äIntroduction and objectives äFacility and process description äPersonnel, planning and scheduling äResponsibilities of validation team members äProcess control aspects äEquipment, apparatus, processes and systems qualified, validated – and to be qualified or validated äAcceptance criteria äDocumentation, e.g.validation protocols and reports äSOPs äTraining requirements and other elements…

19. Module 4 | Slide 19 of 28 January 2006 Qualification and Validation A qualification or validation protocol may contain: äObjectives of the validation and qualification study äSite of the study äResponsible personnel äDescription of the equipment äSOPs äStandards äCriteria for the relevant products and processes (See WHO formats (handouts) as part of training material)

20. Module 4 | Slide 20 of 28 January 2006 Qualification and Validation A qualification or validation report should reflect the elements of the protocol, and may contain elements such as: äTitle äObjective of the study äReference to the protocol äDetails of materials, equipment, instruments, personnel äProgrammes and cycles used äDetails of procedure and test methods … etc.

21. Module 4 | Slide 21 of 28 January 2006 Qualification and Validation Group Session 1: Option 1 lFrom your experience of factory inspections, what progress has been made in introducing validation in your country? lWhat are the major obstacles and how can they be overcome?

22. Module 4 | Slide 22 of 28 January 2006 Qualification and Validation Group Session 1: Option 2 lList some documents related to validation, that you expect to find at a manufacturing site lIdentify aspects in each document that you would evaluate or assess lWhat problems do you anticipate the company faced when it prepared these documents?

23. Module 4 | Slide 23 of 28 January 2006 Qualification and Validation Possible Issues lLack of time lLack of personnel lLack of experience and knowledge lChanges to the process lProspective versus retrospective validation lLack of documentation infrastructure lLack of implementation of validation lPoorly designed documents

24. Module 4 | Slide 24 of 28 January 2006 Qualification and Validation Group Session 2 lList the aspects that you will evaluate when assessing the validation for the project that your group has been given lIdentify the critical parameters that should have been evaluated by the manufacturer lList the tests to be carried out and comment on the acceptance criteria to be set

25. Module 4 | Slide 25 of 28 January 2006 Qualification and Validation Possible situation – I lRefurbishment of a liquids department, producing a single product on an established site with an existing purified water system lVentilation system äEquipment and process äTraining

26. Module 4 | Slide 26 of 28 January 2006 Qualification and Validation Possible situation – II lNew product introduced into an existing tablet manufacturing site, with 20 products already being produced äProcess Cleaning äTraining

27. Module 4 | Slide 27 of 28 January 2006 Qualification and Validation Possible situation – III lA new liquids manufacturing building on an existing site which will produce 2 products äVentilation äEquipment and process äCleaning äTraining

28. Module 4 | Slide 28 of 28 January 2006 Qualification and Validation Possible situation – IV lAn existing sterile suite producing 5 products that are terminally sterilized äSterilizers äVentilation and other environmental aspects äEquipment and process äCleaning äTraining