Design Qualification. DQ Regulatory Requirements EU-GMP, Annex 15

Transcription

1 Design Qualification by Dr. Ingrid Walther May 2015, page 1 DQ Regulatory Requirements EU-, Annex 15 Design qualification (DQ) 3.3. The next element* in the qualification of equipment, facilities, utilities, or systems is DQ where the compliance of the design with should be demonstrated and documented. The requirements of the user requirements specification should be verified during the design qualification. *after URS! What does this mean? DQ is done for the planning status equipment is not yet purchased, installed or in any way present on site! Check and document that what you are going to buy will fulfill all your requirements (URS! This should include all requirements!) Glossary: Design qualification (DQ). The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose. May 2015, page 2

2 DQ Regulatory Requirements WHO 4. Qualification and validation 4.1 In accordance with, each pharmaceutical company should identify what qualification and validation work is required to prove that the critical aspects of their particular operation are controlled. 4.2 VMP 4.3 Qualification and validation should establish and provide documentary evidence that: (a) the premises, supporting utilities, equipment and processes have been designed in accordance with the requirements for (design qualification or DQ); May 2015, page 3 ISPE Guide Volume 5, Commissioning and Qualification Enhanced Design Review (EDR): A structured review of the design of facilities, utilities and equipment is considered by the authors of this guide to be the smart way to prepare for IQ and OQ activities. It is in the interests of all to reveal design or specification problems through a rigorous, structured review process early in a project, rather than discover them later at the IQ or OQ stages, where a remedy might involve significant delay and expense. This, however, remains a business risk driven choice, not a regulatory expectation. In general, EDR may be considered as equivalent to Design Qualification US-FDA: no official requirement but in general expected as common practice Common Practice: EDR / DQ for -compliance and economic reasons May 2015, page 4

3 When is DQ performed? Before signing the purchasing order! Basic RA Detail RA Engineering Manufacturing Delivery/ Installation Commissioning Test Runs/ Start-up Process Optimisation Production URS DQ/FDS FAT IQ/SAT OQ PQ PV / CV Re-Val. Change Control / Requalification May 2015, page 5 DQ - For which equipment, facilities, systems? Which project documents should undergo Design Qualification? Specifications for critical systems and components Equipment and systems Components Instruments Computerised Systems Installation Work Cleaning Work after installation etc. Diagrams (Layouts / P&ID s / Drawings) System Design Line Design Personnel and material flow etc. Keep in mind: DQ is about documents, it is done in the planning phase! May 2015, page 6

4 Relationship between Systems and Components : a system in general consists of different components components may be critical or non-critical if a system has one critical component, it has to be considered as direct impact valve sensor valve Vessel piping sensor System valve valve Component pump May 2015, page 7 Relationship between Systems and Components : What has to be considered in DQ?! Direct Impact Systems, because: a DI system has to undergo qualification indirect impact / non-critical components undergo commissioning Valve Sensor Valve Vessel Piping Sensor Direct Impact System critical Component non-critical Component Valve Pump Valve May 2015, page 8

5 Relationship between Systems and Components : If a system has one critical component it is a critical, DISystem ISPE Baseline: Figure 3-2 May 2015, page 9 DQ-Execution for Systems What is -relevant in a system? components the system itself! DQ Execution for a System: System Step 1: DQ for Components Vessel Valves Instruments Piping Step 2: DQ for the System Check availability of DQ for the components Check arrangement and connection of the components May 2015, page 10

6 DQ-Execution Results of the RA (-relevant requirements) and general requirements! DQ-Test-Points Approval of the test points (may be done by approving the RA!) Results (including deficiencies) are documented If DQ-requirements are fulfilled! Approval of DQ-Report... for Components (Specification Qualification) DQ-Test-Plan is compared / crosschecked against FDS Use URS/FRS = DQ-Requirements RA = DQ-Protocol DQ-Protocol! DQ-Report URS! FDS-cross-check RA! FRS/ FDS-cross-check for Systems (Units / Lines /...) DQ-Test-Plan (e.g. Check-List) is compared / cross-checked against Drawings DQ-Protocol! DQ-Report May 2015, page 11 Some practical hints for URS / RA and DQ Compare URS with FDS Prepare a Draft URS, evolve by RA, compare URS with FDS May 2015, page 12

7 Some practical hints for URS / RA and DQ Evolve URS to Functional Requirement Specification and compare with FDS... 2-step DQ May 2015, page 13 How to handle good suggestions of the supplier? Check, if they are in conflict with -requirements! DQ-Requirements No. 1. AAA 2. BBB 3. CCC 4. DDD 5. EEE 6. FFF 7. GGG 8. HHH Requirement Supplier s FDS Parameters No. 1. AAA 2. BBB 3. CCC 4. DDD 5. EEE 6. FFF 7. GGG 8. HHH 9. JJJ 10. KKK 11. LLL conflict with the -requirements? May 2015, page 14

8 Some practical hints for URS / RA and DQ Evolve URS to Functional Requirement Specification and compare with FDS... and cross-check by RA (involvement of suppliers may be useful) May 2015, page 15 DQ-Execution Contract Specification Commercial Aspects Technical Aspects (FDS) Functional Aspects Safety/Environmental Aspects without relevance with relevance without relevance with relevance = relevant for DQ May 2015, page 16

9 How to perform the DQ based on the URS Draft-URS! needs to undergo RA These elements need to be checked in DQ May 2015, page 17 User Requirement Specification a new requirement! Check the defined requirements by an RA May 2015, page 18

10 How to perform the DQ URS Final Version (FRS)! submitted to suppliers for quotation fields for results of cross-checking with FRS or URS FDS (from supplier) reference to RA for traceability May 2015, page 19 Is it a lot of additional effort to perform a DQ? No, because in DQ, you should cover (most) IQ and OQ/PQ- Test-Points: DQ-Test Points Documentation and Installation Aspects Functional and Safety Aspects IQ-Test Points OQ/PQ-Test Points May 2015, page 20

11 Traceability of -Requirements and s RA has to be modified in case of changes! IQ:!!!! OQ: PQ: URS! RA! DQ! FDS! Qualification May 2015, page 21 How to perform DQ for layouts? Checklists prepared on the basis of the URS (challenged and confirmed by RA!) Have requirements indicated precisely! No. User Requirement Fulfilled by Layout Version No. Date: y / n Remarks; e.g. indicate location, etc. 1 Airlocks 1.1 Female airlock from Grade CNC! D is sufficient for 20 persons 1.2 Male airlock from Grade CNC! D is sufficient for 20 persons 1.3 Female airlock from Grade D! B is a two-chamber airlock 1.4 The way into the airlock is separated from the way out of the airlock 2 Separation of the areas 2.1 The areas between operations before and after virusinactivation are clearly separated 2.2 The ways for dirty equipment are separated from the ways for clean equipment 3 Pressure Concept 3.1 There are pressure differences between the different clean room Grades of 15 Pa 3.2 The pressures are in general higher in cleaner zones 3.3 There are no areas where pressure differences between adjacent rooms are more than 50 Pa. May 2015, page 22

12 After DQ! Change Control 2.6 Any changes to the approved protocol during execution should be documented as a deviation and be scientifically justified. " justification for changes required scientifically justified may be very difficult to achieve. Based on knowledge, experience and sound conclusions? " A change to a document may be done on the basis of change control! required after DQ, the point when a qualified status was achieved. Basic RA Detail RA DQ = qualified status! required Change Control Engineering Manufacturing Delivery/ Installation Commissioning Test Runs/ Start-up Process Optimisation Routine Production URS DQ/FDS FAT IQ/SAT OQ PQ PV / CV Re-Val. Change Control / Requalification - Revalidation May 2015, page 23 After DQ! Change Control Good Practices in Documentation Good Engineering Practice / DQ -CC -CC GEP GEP GEP Project Execution Routine Use Maintaining the qualified state May 2015, page 24

13 Advantages provided by DQ " -relevant requirements are defined in the specification phase (before the equipment is ordered!)! Unexpected -problems in later qualification phases become unlikely. Economic Aspect! " -relevant requirements fixed in DQ-Protocols! Preparation of IQ/ OQ/ PQ-protocols easy Disadvantage : Much theoretical work at an early project phase! May 2015, page 25 Contact: Pharma Consulting Walther Dr. Ingrid Walther Rosenweg Friedrichsdorf Germany +49-(0) (0) iw@consulting-walther.com Disclaimer: This presentation has been prepared upon best knowledge and it presents the view and experience of Pharma Consulting Walther. The presentation reflects current guidelines, knowledge and thinking. Changes of regulatory guidelines or interpretation thereof or new regulatory expectations may change the applicability of the contents of this presentation. Parts of the presentation may not be understood or misinterpreted without the verbal explanation given during the seminar. Although the statements made in the presentation in general have been presented to and discussed with inspectors, a different approach may be required and adequate depending on the individual situation. The information contained herein may be changed without prior notice. May 2015, page 26