World Health Organization 29 April, 2018 Supplementary Training Modules on Good Manufacturing Practice Validation In this supplementary training module, we will be looking at the recommendations by WHO, on Validation and qualification. The module consists of 7 parts: Part 1. General overview on qualification and validation Part 2. Qualification of HVAC and water systems Part 3. Cleaning validation Part 4. Analytical method validation Part 5. Computerized system validation Part 6. Qualification of systems and equipment Part 7. Non sterile product process validation Each part deals with a specific topic, and each part can be presented in about one to one and a half hours time. Presenters should know the topics and add practical examples to the texts taken from the WHO guideline. WHO Technical Report Series, No. 937, 2006. Annex 4.

World Health Organization Validation 29 April, 2018 Part 1. General overview on qualification and validation Part 2. Qualification of HVAC and water systems Part 3. Cleaning validation Part 4. Analytical method validation Part 5. Computerized system validation Part 6. Qualification of systems and equipment Part 7. Non sterile product process validation

World Health Organization 29 April, 2018 Supplementary Training Modules on Good Manufacturing Practice Qualification of systems and equipment Part 6 WHO Technical Report Series, No. 937, 2006. Annex 4. Appendix 6.

World Health Organization Validation World Health Organization 29 April, 2018 Objectives To discuss the principles of qualification of systems and equipment, with specific focus on: The different stages of qualification Requalification and Qualification of “in use” systems and equipment Qualification of systems and equipment 1. Principle 2. Scope 3. General 4. Design qualification 5. Installation qualification 6. Operational qualification 7. Performance qualification 8. Requalification 9. Qualification of “in use” systems and equipment

World Health Organization Validation 29 April, 2018 Principle Systems and equipment: Appropriately designed, located, installed, operated and maintained Critical systems and equipment – should be qualified May include, where appropriate: Water purification systems, air-handling systems, autoclaves, coating machines Continued suitable performance needed Why? To ensure batch-to-batch consistency Principle 1.1 Systems and equipment should be appropriately designed, located, installed, operated and maintained to suit their intended purpose. 1.2 Critical systems, i.e. those whose consistent performance may have an impact on the quality of products, should be qualified. These may include, where appropriate, water purification systems, air-handling systems, compressed air systems and steam systems. 1.3 The continued suitable performance of equipment is important to ensure batch-to-batch consistency. Critical equipment should therefore be qualified. 1.1 – 1.3

World Health Organization Validation 29 April, 2018 Scope Guidelines describe the general aspects of qualification for systems and equipment Normally qualification would be applicable to critical systems and equipment whose performance may have an impact on the quality of the product Scope Guidelines describe the general aspects of qualification for systems and equipment. Normally qualification would be applicable to critical systems and equipment whose performance may have an impact on the quality of the product. 2.1 – 2.2

World Health Organization Validation 29 April, 2018 General Qualification policy for systems and equipment To include instruments used in production and quality control New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ) In some cases: Not all stages of qualification may be required e.g. electrical supply systems General Qualification policy for systems and equipment. To include instruments used in production and quality control. New systems and equipment: All stages of qualification applicable (DQ, IQ, OQ and PQ). In some cases: Not all stages of qualification may be required. E.g. electrical supply systems. 3.1 – 3.4

World Health Organization Validation 29 April, 2018 General (continued) Systems: Qualified before equipment Equipment: Qualified before routine use Systems and equipment: Periodic requalification, as well as requalification after change Certain stages done by the supplier or a third party Maintain the relevant documentation, e.g. standard operating procedures (SOPs), specifications and acceptance criteria, certificates and manuals Systems should be qualified before equipment. 3.6 Equipment should be qualified prior to being brought into routineuse to provide documented evidence that the equipment is fi t for its intended purpose. 3.7 Systems and equipment should undergo periodic requalification, as well as requalification after change. 3.8 Certain stages of the equipment qualification may be done by the supplier or a third party. 3.9 The relevant documentation associated with qualification including standard operating procedures (SOPs), specifications and acceptance criteria, certificates and manuals should be maintained. 3.10 Qualification should be done in accordance with predetermined and approved qualification protocols. The results of the qualification should be recorded and reflected in qualification reports. 3.11 The extent of the qualification should be based on the criticality of a system or equipment (e.g. blenders, autoclaves or computerized systems).S 3.5 – 3.9

World Health Organization Validation 29 April, 2018 General (continued) Qualification should be done in accordance with predetermined and approved qualification protocols The results of the qualification should be recorded and reflected in qualification reports The extent of the qualification should be based on the criticality of a system or equipment, e.g. Blenders, autoclaves or computerized systems 3.10 Qualification should be done in accordance with predetermined and approved qualification protocols. The results of the qualification should be recorded and reflected in qualification reports. 3.11 The extent of the qualification should be based on the criticality of a system or equipment (e.g. blenders, autoclaves or computerized systems). 3.10 – 3.11

World Health Organization Validation World Health Organization 29 April, 2018 Blender Discuss the approach of qualification of a newly installed blender The trainer should invite discussion from participants on the approach, stages, parameters to be considered in the qualification of equipment. Use examples of pieces of equipment.

World Health Organization Validation World Health Organization 29 April, 2018 Stages of qualification Design qualification Installation qualification Operational qualification Performance qualification Stages of qualification There are generally, four stages in qualification. Can you name them? Design qualification Installation qualification Operational qualification Performance qualification Change control We will look into more detail on these stages in the next slides. 3.11

World Health Organization Validation World Health Organization 29 April, 2018 Stages of qualification Design qualification Installation qualification Operational qualification Change control Performance qualification Stages of qualification There are generally, four stages in qualification. Can you name them? Design qualification Installation qualification Operational qualification Performance qualification Change control We will look into more detail on these stages in the next slides. 3.11.

World Health Organization Validation 29 April, 2018 Design qualification User requirements should be considered when deciding on the specific design of a system or equipment A suitable supplier should be selected for the appropriate system or equipment (approved vendor) Design qualification User requirements should be considered when deciding on the specific design of a system or equipment. A suitable supplier should be selected for the appropriate system or equipment (approved vendor). 4.1 – 4.2

World Health Organization Validation 29 April, 2018 Installation qualification Correct installation as per plan and protocol Normally advised to prepare requirements for calibration, maintenance and cleaning at this stage Identification and verification of all system elements, parts, services, controls, gauges and other components Calibrate the measuring, control and indicating devices against appropriate, traceable national or international standards Installation qualification 5.1 Systems and equipment should be correctly installed in accordance with an installation plan and installation qualification protocol. 5.2 Requirements for calibration, maintenance and cleaning should be drawn up during installation. 5.3 Installation qualification should include identification and verification of all system elements, parts, services, controls, gauges and other components. 5.4 Measuring, control and indicating devices should be calibrated against appropriate national or international standards, which are traceable. 5.1 – 5.4

World Health Organization Validation 29 April, 2018 Installation qualification (2) Documented records for the installation installation qualification report Indicate satisfactory installation Include details, e.g. The supplier and manufacturer System or equipment name, model and serial number Date of installation Spare parts, relevant procedures and certificates 5.5 There should be documented records for the installation (installation qualification report) to indicate the satisfactoriness of the installation, which should include the details of the supplier and manufacturer, system or equipment name, model and serial number, date of installation, spare parts, relevant procedures and certificates. 5.5

World Health Organization Validation 29 April, 2018 The handout shows a typical format for "An installation qualification protocol / report" It reflects the minimum information that should be included This is an example – and should be used as such Specific formats need to be designed for a specific system or piece of equipment 5.5

World Health Organization Validation 29 April, 2018 Operational qualification Systems and equipment should operate correctly – operation verified as in the qualification protocol Studies on critical variable to include conditions encompassing upper and lower operating limits and circumstances (i.e. “worst case conditions”) To include verification of operation of all system elements, parts, services, controls, gauges and other components Operational qualification Systems and equipment should operate correctly - operation verified as in the qualification protocol. Studies on critical variable to include conditions encompassing upper and lower operating limits and circumstances (that is “worst case conditions”). To include verification of operation of all system elements, parts, services, controls, gauges and other components. 6.1 – 6.3

World Health Organization Validation 29 April, 2018 Operational qualification (2) Documented records (Operational qualification report) Finalize and approve SOP (operation) Training of operators provided – training records Systems and equipment released for routine use after completion of operational qualification, provided that: All calibration, cleaning, maintenance, training and related tests and results were found to be acceptable 6.4 There should be documented records for the verification of operation (operational qualification report) to indicate the satisfactory operation. 6.5 Standard operating procedures for the operation should be finalized and approved. 6.6 Training of operators for the systems and equipment should be provided, and training records maintained. 6.7 Systems and equipment should be released for routine use after completion of operational qualification, provided that all calibration, cleaning, maintenance, training and related tests and results were found to be acceptable. 6.4 – 6.7

World Health Organization Validation 29 April, 2018 The handout shows a typical format for: "An operational qualification protocol / report" It reflects the minimum information that should be included This is an example – and should be used as such Specific formats need to be designed for a specific system or piece of equipment 6.7

World Health Organization Validation 29 April, 2018 Performance qualification Systems and equipment should consistently perform in accordance with design specifications – verified in accordance with a performance qualification protocol Documented records – performance qualification report Show satisfactory performance over a period of time Manufacturers to justify the selected period Performance qualification Systems and equipment should consistently perform in accordance with design specifications - verified in accordance with a performance qualification protocol. Documented records - performance qualification report. Show satisfactory performance over a period of time. Manufacturers to justify the selected period. 7.1 – 7.2

World Health Organization Validation 29 April, 2018 The handout shows a typical format for: "A performance qualification protocol / report" It reflects the minimum information that should be included This is an example – and should be used as such Specific formats need to be designed for a specific system or piece of equipment 7.2

World Health Organization Validation World Health Organization 29 April, 2018 Defined schedule Periodic Requalification After change The manufacturer should have a policy on requalification. It should cover periodic requalification as well requalification after change. 8.1 – 8.3

World Health Organization Validation 29 April, 2018 Defined schedule Results of calibration maintenance, verification Frequency based on Factors Periodic Requalification After change Extent based on Risk assessment Requalification 8.1 Requalification of systems and equipment should be done in accordance with a defined schedule. The frequency of requalification may be determined on the basis of factors such as the analysis of results relating to calibration, verification and maintenance. 8.2 There should be periodic requalification. 8.3 There should be requalification after changes. The extent of requalification after the change should be justified based on a risk-assessment of the change. Requalification after change should be considered as part of the change control procedure. Part of Change control procedure 8.1 – 8.3

World Health Organization Validation 29 April, 2018 What about "old manufacturers" who have not performed DQ, or IQ for existing, in-use systems and/or equipment?

World Health Organization Validation 29 April, 2018 Qualification of “in-use” systems and equipment Data to support and verify the suitable operation and performance of systems and equipment Should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records Qualification of “in-use” systems and equipment The manufacturer should have data to support and verify the suitable operation and performance of systems and equipment. This should include operating parameters and limits for critical variables, calibration, maintenance and preventive maintenance, standard operating procedures (SOPs) and records. On the basis of this, OQ and PQ could be done (protocol and reports prepared). Remember – can still do requalification! 9.1 – 9.2

World Health Organization Validation World Health Organization 29 April, 2018 Group session (Example) The trainer could ask the participants to discuss the approach of qualification for a piece of equipment. Present the participants with a schematic drawing of equipment, or a manual and related documentation, and ask them to discuss key aspects in the different stages of qualification.

World Health Organization Validation World Health Organization 29 April, 2018 Group session The presenter should prepare case studies for the groups on qualification of systems and equipment. Participants could discuss qualification requirements for systems e.g. steam generators for autoclaves, qualification of critical equipment including coating machines, compression machines, autoclaves, dry heat sterilizers etc.