GAMP 4/5 Prospective / retrospective Qualification of water treatment plants) P. Dony

Transcription

1 GAMP 4/5 Prospective / retrospective Qualification of water treatment plants) P. Dony

2 Table of contents Slide 2 1. GAMP 4 and GAMP 5 differences 2. CHRIST prospective Qualification strategy 3. CHRIST retrospective Qualification strategy

3 1. GAMP 4 and GAMP 5 differences Slide 3 Why revision of GAMP 4: To align with the concepts and terminology of recent regulatory and industry developments such as: - ICH Q 9 (Annex 20) - FDA: Pharmaceutical cgmps for the 21st Century: A Risk based Approach Avoid duplication of activities Leverage supplier activities to the maximum possible extent, while still ensuring fitness for intended use Scale all life cycle activities and associated documentation according to risk, complexity and novelty Recognize that most computerized systems are now based on configurable packages, many of them networked

4 1. GAMP 4 and GAMP 5 differences Slide 4 Drivers for GAMP 5

5 1. GAMP 4 and GAMP 5 differences Slide 5 Overview of the significant changes GAMP 4 to GAMP 5 GAMP 5 now describes the whole life cycle (including: concept, project, operation, retirement) GAMP 5 arranges the Quality risk management as a central element in all phases of the life cycle GAMP 5 was aligned with the ASTM E2500 and the ISPE Baseline-Guide Commissioning and Qualification terminology GAMP 5 now gives the suppliers a key role in the development processes and in the operation processes GAMP 5 has simplified the GAMP categories, Chapters of the GAMP 4 which describes special types of computer systems were canceled BUT: The GAMP 5 remains compatible with the principles in GAMP 4

6 1. GAMP 4 and GAMP 5 differences Slide 6 Life Cycle The general simplified Life Cycle:

7 1. GAMP 4 and GAMP 5 differences Slide 7 Life Cycle Phases

8 1. GAMP 4 and GAMP 5 differences Slide 8 Quality Risk Management (QMS): The QMS is a systematic approach for the assessment, control, communication and review of risks to patient safety, product quality and data integrity. It is an iterative process applied throughout the entire system life cycle. Section 5 describes this approach and how the activities should be based on good science and product and process understanding. Benefit of the risk based approach: Better knowledge about the processes and because of that a better process control (also described in ICH Q8 (QbD), ICH Q9 (QMS), ICH Q10 (PQS)) Safeguard patient safety, product quality, and data integrity, while also delivering business benefit A central element to reducing the validation effort by concentrating on the most critical processes and therewith reducing the validation costs

9 1. GAMP 4 and GAMP 5 differences Slide 9 Aligned terminology The classical nomenclature of IQ, OQ and PQ are not longer used in GAMP 5 Implementation of the word verification instead of the classical nomenclature Focusing of the contents of the created documents not longer of the nomenclature. But also the classical nomenclature can be used Unification of the following Guidelines: - FDA: Pharmaceutical cgmps for the 21st Century: A Risk based Approach - ASTM E GAMP 5 - ISPE Baseline-Guide Commissioning and Qualification

10 1. GAMP 4 and GAMP 5 differences Slide 10 Key role of the suppliers Ensuring compliance and fitness for purpose is the responsibility of the regulated company The supplier gets more liberties, but also more responsibilities The supplier gets the liberty to carry out the system development in accordance of accepted development- and quality management methods (e.g. ISO 9000) without consideration of specific GxP requirements Documentation of the suppliers can be taken directly and without changing the format in the validation documentation of the regulated company (no duplication) Services of the suppliers should be overtaken considerable as possible (in specification and verification processes)

11 1. GAMP 4 and GAMP 5 differences Slide 11 Confrontation GAMP 4 and GAMP 5 referring to the suppliers role GAMP 4 GAMP 5 Chapter Supplier Assessment and Education Chapter 7 Supplier activities Chapter 7.2 Supplier good practice activities Chapter 8 Management System for Suppliers of IT Systems Appendix M 2 Guideline for Supplier Audit Chapter 8.3 Effective supplier participation Appendix M 2 Supplier Assessment Appendix M 6 Supplier Quality and Project Planning Appendix O 2 Example Procedure for the Production of a Service Level Agreement Appendix O 2 Establishing and Managing Support Service

12 1. GAMP 4 and GAMP 5 differences Slide 12 GAMP 5 Main Body Structure Key Concepts Life Cycle Approach Life Cycle Phases Concept Project Operation Retirement Science Based Quality Risk Management Regulated Company Activities Governance for Achieving Compliance System Specific Activities Supplier Activities Efficiency Improvements

13 1. GAMP 4 and GAMP 5 differences Slide 13 Main Changes of the GAMP 5 appendices

14 1. GAMP 4 and GAMP 5 differences Slide 14 Main Changes of the GAMP 5 appendices

15 1. GAMP 4 and GAMP 5 differences Slide 15 Main Changes of the GAMP 5 appendices

16 1. GAMP 4 and GAMP 5 differences Slide 16 GAMP Software Categories Category 1 GAMP 4 Operating system Ifrastructure software GAMP Firmware Standard software No longer used (Firmware is no longer functionally distinguishable) Non-configured software 4 5 Configurable software packages Custom software Configured software (supplier assessments rather than audits) Custom software (supplier assessments rather than audits

17 1. GAMP 4 and GAMP 5 differences Slide 17 Size of verification software category 3

18 1. GAMP 4 and GAMP 5 differences Slide 18 Size of verification software category 4

19 1. GAMP 4 and GAMP 5 differences Slide 19 Size of verification software category 5

20 1. GAMP 4 and GAMP 5 differences Slide 20 Movements and Benefits Reduction of validation costs (as a result of the risk based approach and a stronger comprehension of the suppliers activities) A better process acknowledgement (on side of the regulated company and on side of the suppliers) More flexibility of improvements (simplification of the validation process)

21 2. CHRIST prospective Qualification strategy Slide 21 V-Model URS Requirements of the User PQ FDS Affirmation of the Requirements of the supplier OQ Technical Specifications IQ Manufacturing of the Equipment

22 2. CHRIST prospective Qualification strategy Slide 22 The CHRIST Qualification Conception The validation shall show that the water treatment system is installed correctly according to the design specification and that the system works correctly. The validation is divided in two sections: FAT Factory Acceptance Test SAT Site Acceptance Test In each section (FAT and SAT), both installation inspections (IQ) and functional inspections (OQ) are carried out. In order to reduce the time needed for on-site qualification, as many inspections and tests as possible are executed during the FAT, before the system leaves the factory. CHRIST has a special test bed and can, in most cases, also carry out test runs of the system before it is dispatched.

23 2. CHRIST prospective Qualification strategy Slide 23 DQ-Documents: Order Confirmation (FDS) (or optional customized FDS) Risk analysis (FMEA iterative) Quality and project plan (QPP) (optional) Technical Specifications P&ID List of Components Hardware Specifications Circuit Diagram Hardware Design Specification (HDS) Software Specifications Functional Logic (FL) Software Design Specification (SDS)

24 2. CHRIST prospective Qualification strategy Slide 24 Example P&ID

25 2. CHRIST prospective Qualification strategy Slide 25 Example of Risk analyses (iterative)

26 2. CHRIST prospective Qualification strategy Slide 26 IQ Tests during FAT 1. Inspection of the Mechanical Installation and the Documentation P&ID: Check that the water treatment system is built according to the P&ID Component list: Check that all components of the system are in accordance with the list of components Manuals and Data Sheets: Check manuals and data sheets from the sub-supplier Certificates for components: Check the certificates (which are specified in the list of components) for all components Dead-Legs: Check that no dead-legs are present on the product side (3d or 6d rule) Air gap to drain: Check by visual inspection that the pipe to drain leaves an air gap to the drainage. Welding documentation: Check that the welding documentation for the water treatment system (including certificates for pipes and fittings) is present and complete.

27 2. CHRIST prospective Qualification strategy Slide 27 IQ Tests during FAT 2. Inspection of the Electrical Hardware (Hardware Acceptance Test) Inspection of the switchgear cabinet: Check that the inspection record sheet for the switchgear cabinet is completely filled out and that the document is signed and dated. Line test: Check that the line test inspection sheet (external cables, digital inputs and outputs, analogue inputs and outputs) is completely filled out and that the document is signed and dated. Main switch: Check the consequence of power failure (simulation through the main switch)

28 2. CHRIST prospective Qualification strategy Slide 28 OQ Tests during FAT 1. Inspection of the Software (System Acceptance Test) Functional logic: Check the software and program steps together with the related controllers, special logics and system parameters according to the functional logic. Alarms: Check the alarms according to the functional logics. Password: Check the access authority for different password levels.

29 2. CHRIST prospective Qualification strategy Slide 29 IQ Tests during SAT 1. Inspection of the Mechanical Installation and the Documentation FAT Completion: Check if the retests and the deviations from the FAT are performed Documentation for the water treatment system: Check that the documentation for the system is present P&ID: Check that the system is built according the P&ID and that the items are marked with the correct P&ID number List of components: Check that all components of the system are in accordance with the list of components Air gap to drain: Check by visual inspection that the pipe to drain leaves an air gap to the drainage. Dead-Legs: Check that no dead-legs are present on the product side (3d or 6d rule) Gradients (for distribution system): Check that the piping of the loop has been installed with the requested downward gradient Drainability (for distribution system): Check that the loop can be drained at its lowest points.

30 2. CHRIST prospective Qualification strategy Slide 30 IQ Tests during SAT 2. Inspection of the Electrical Hardware (if not already checked during FAT) Check the external cables and the analogue inputs and outputs Main switch: Check the consequence of power failure (simulation through the main switch)

31 2. CHRIST prospective Qualification strategy Slide 31 OQ Tests during SAT 1. Inspection of the Software (System Acceptance Test) Software-Version: Check the software versions of the HMI / PLC program and for the programming tools Backup: Preparation of a backup of the used program (Back-up disc or CD-Rom.)

32 2. CHRIST prospective Qualification strategy Slide 32 OQ Tests during SAT 2. Functional Tests Leaks test: Check the plant connections and the components for leaks Operation of the Softener: Check the performance parameter of the softener, logging of the main operating data Operation of the RO: Check the performance parameter of the reverse osmosis Operation of the EDI: Check the performance parameter of the EDI Operation of the dosing units (wherever applicable): Check the dosing units and the regulations Operation of the storage and distribution system components: Check the performance parameter of the components (e.g. ozone generator, ozone measurement, UV unit) Function of regulation circuits (wherever applicable): Check the regulation circuits of the system System parameter: Logging of all actual system parameter Water Quality: Check the water quality (conductivity, TOC * and Microbiological situation*(* = analysis by customer))

33 2. CHRIST prospective Qualification strategy Slide 33 PQ Plan First phase Development of the operational parameters Development of the cleaning / sanitization procedures and frequencies Sampling should be daily after each step in the purification process and at each point of use The sampling procedure for point of use sampling should reflect how the water is to be drawn (e.g. if a hose is usually attached the sample should be taken at the end of the hose) Length: two to four weeks At the end of this phase the firm should have developed its SOPs for operation of the water system

34 2. CHRIST prospective Qualification strategy Slide 34 PQ Plan Second phase Demonstration that the system will consistently produce the desired water quality when operated in conformance with the SOPs Same sampling as in the first phase and for the same time period Length: also two to four weeks

35 2. CHRIST prospective Qualification strategy Slide 35 PQ Plan Third phase Demonstration that the water system will consistently produce the desired water quality when operated in accordance with the SOPs over a long period of time Any variations in the quality of the feedwater (seasonal variations) that could affect the operation and ultimately the water quality will be picked up Sampling is performed according to routine procedures and frequencies For WFI systems the samples should be taken daily from a minimum of one point of use, with all points of use tested weekly Length: one Year The last part of the validation is the compilation of the data, with any conclusions into the final report.

36 2. CHRIST prospective Qualification strategy Slide 36 PQ Plan structure Introduction Intention of the performance qualification Abbreviations Manifestations at execution of the performance qualification Table of persons participating in the inspection Execution of the PQ Preface Point of use / sampling points Analyzing Parameters Water sampling from the system Arrangements Off-limit conditions (OOS/OOT Results) Summary report

37 3. CHRIST retrospective Qualification strategy Slide 37 When you have to do a retrospective Qualification Existing Systems which are in operation without any qualification up to now Existing Systems which are in operation without an adequate qualification up to now

38 3. CHRIST retrospective Qualification strategy Slide 38 Condition contrary to regulations only acceptable for well-established processes inappropriate where there have been recent changes in the composition of the product, operating procedures or equipment should be based on historical data (which are evaluated in a protocol) This data could include process control charts, maintenance log books, process capability studies, finished product data Basically retrospective qualifications has the same inspection scope like prospective qualification

39 3. CHRIST retrospective Qualification strategy Slide 39 Procedure of a retrospective qualification Audit of the existing high purity water system Qualification Check Documentation Check Mechanical Check Electrical Check Functional Check Software Check Report of the audit Description of the System Description of the critical results Scaling of the critical results Further approach (required qualification documents and proposal to eliminate the critical points)

40 3. CHRIST retrospective Qualification strategy Slide 40 Procedure of a retrospective qualification Qualification Check Has been carried out a qualification before? When the last qualification was carried out? Has been all deviations removed? Was the qualification risk based and adequate realized?

41 3. CHRIST retrospective Qualification strategy Slide 41 Procedure of a retrospective qualification Documentation Check SOP s Analytical studies (Monitoring of the critical batch relevant parameters) Electronic records Log books Drawings (R&I, Layout, circuit diagram) List of components Manuals and datasheets Certificates Operating Instructions (process descriptions) Welding documentation Staff training

42 3. CHRIST retrospective Qualification strategy Slide 42 Procedure of a retrospective qualification Mechanical Check Design of the system and system rating Marked items Air gap s Dead-Legs Gradients (for distribution system) Drain ability (for distribution system) Materials of the critical system components (visual check) Welding Connections Design of the Critical components (valves, heat exchangers, Pumps)

43 3. CHRIST retrospective Qualification strategy Slide 43 Procedure of a retrospective qualification Electrical Check Hardware Design Specification Line test (AI/AO/DI/DO) Switchgear cabinet External cables

44 3. CHRIST retrospective Qualification strategy Slide 44 Procedure of a retrospective qualification Functional Check Functional Logic System parameters Alarm parameters Controllers Calibration CIP/SIP/DIP Functions

45 3. CHRIST retrospective Qualification strategy Slide 45 Procedure of a retrospective qualification Software Check Software Design Specifications (including software classification) Software reviews Password GAMP 4/5 conformity

46 3. CHRIST retrospective Qualification strategy Slide 46 Procedure of a retrospective qualification Possible arrangements to get GxP conform status (some examples) If no data about the material of the critical piping and components: Nondestructive tests If no, or incomplete, or inadequate welding documentation: Try to make on critical welding seams some endoscopic photos If no functional logic: Document the function (including process measuring and control technology) If no circuit diagram: Draw an actual circuit diagram

47 3. CHRIST retrospective Qualification strategy Slide 47 Procedure of a retrospective qualification Possible arrangements to get GxP conform status WFI distribution System: No adequate GxP conform weld seam accomplishment In this case cut out this area

48 3. CHRIST retrospective Qualification strategy Slide 48 Procedure of a retrospective qualification Possible arrangements to get GxP conform status Pure Steam System: No GxP conform ball valves No adequate GxP conform weld seam accomplishment No GxP conform connections In this case make a new POU: Composed of: Diaphragm Valves GxP conform steam trap

49 3. CHRIST retrospective Qualification strategy Slide 49 Procedure of a retrospective qualification Possible arrangements to get GxP conform status WFI Distribution System: Bad weld seam accomplishment In this case cut of both POU and make new ones

50 3. CHRIST retrospective Qualification strategy Slide 50 Procedure of a retrospective qualification Starting to write the following validation Protocols (like prospective strategy): VMP URS (target state) FDS (actual state) RA (Risk based approach very necessary) RA report IQ OQ PQ

51 3. CHRIST retrospective Qualification strategy Slide 51 Procedure of a retrospective qualification Summary The retrospective Qualification is a validation process which must be individual considered (dependent of the system and it s condition) Approach of a retrospective Qualification must be described by the regulated company (SOP, SVMP)

52 Slide 52 Thank you for your Concentration!!!! Any Questions????