design qualification - dcvmn · 4.1 in accordance with gmp, ... it is in the interests of all to...
TRANSCRIPT
May 2015, page 1
Design Qualification
by Dr. Ingrid Walther
May 2015, page 2
DQ – Regulatory Requirements EU-GMP, 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 GMP 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 GMP-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 3
DQ – Regulatory Requirements WHO
4. Qualification and validation 4.1 In accordance with GMP, 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 GMP (design qualification or DQ);
May 2015, page 4
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 GMP-compliance
and economic reasons
May 2015, page 5
Engineering
Manufac- turing
Delivery/ Installation
Commiss-ioning
Test Runs/ Start-up
Process Optimi-sation
DQ/FDS Re-Val. PV / CV OQ FAT URS PQ
Change Control / Requalification
IQ/SAT
Detail RA Basic RA
Production
When is DQ performed?
Before signing the purchasing order!
May 2015, page 6
DQ - For which equipment, facilities, systems?
• 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.
Which project documents should undergo Design Qualification?
Keep in mind: DQ is about documents, it is done in the planning phase!
May 2015, page 7
Relationship between “Systems” and “Components”:
Component
System
• 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”
Vessel
piping
valve
valve valve
valve
sensor
sensor
pump
May 2015, page 8
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
Vessel
Piping
Valve
Valve Valve
Valve
Sensor
Sensor
Pump non-critical Component
critical Component
Direct Impact System
May 2015, page 9
Relationship between “Systems” and “Components”: If a system has one critical component – it is a critical, DI-System
ISPE Baseline: Figure 3-2
May 2015, page 10
System
DQ Execution for a 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
DQ-Execution for Systems What is GMP-relevant in a system? • components • the system itself!
May 2015, page 11
• DQ-Test-Plan is compared / cross-checked against FDS
• Use URS/FRS = DQ-Requirements
• RA = DQ-Protocol
... for Components (Specification Qualification)
DQ-Protocol ! DQ-Report
URS ! FDS-cross-check
RA ! FRS/ FDS-cross-check
DQ-Execution
• DQ-Test-Plan (e.g. Check-List) is compared / cross-checked against Drawings
DQ-Protocol ! DQ-Report
… for Systems (Units / Lines / ...)
• Results of the RA (GMP-relevant requirements) and general GMP-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
May 2015, page 12
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 13
Some practical hints for URS / RA and DQ
Evolve URS to Functional Requirement Specification and compare with FDS
.... 2-step DQ
May 2015, page 14
How to handle „good suggestions“ of the supplier? Check, if they are in conflict with GMP-requirements!
DQ-Requirements
No.
Requirement
1. AAA 2. BBB 3. CCC 4. DDD 5. EEE 6. FFF 7. GGG 8. HHH
Supplier‘s FDS
No. Parameters 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 GMP-requirements?
May 2015, page 15
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 16
DQ-Execution
Contract Specification
Functional Aspects
Technical Aspects (FDS)
Commercial Aspects
without GMP-relevance
Safety/Environmental Aspects
with GMP- relevance
without GMP-relevance
with GMP- relevance
= relevant for DQ
May 2015, page 17
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 18
User Requirement Specification – a new requirement!
Check the defined requirements by an RA
May 2015, page 19
How to perform the DQ
URS Final Version (FRS) ! submitted to suppliers for quotation
fields for results of cross-checking with FRS or URS
reference to RA for traceability
FDS (from supplier)
May 2015, page 20
DQ-Test Points
IQ-Test Points
OQ/PQ-Test Points
Documentation and Installation Aspects
Functional and Safety Aspects
No, because in DQ, you should cover (most) IQ and OQ/PQ-Test-Points:
Is it a lot of additional effort to perform a DQ?
May 2015, page 21
CPP GMP
CPP GMP
CPP GMP
CPP GMP
! ! !
FDS DQ RA URS ! ! !
Traceability of GMP-Requirements and CPPs RA has to be modified in case of changes!
IQ: CPP GMP
OQ: CPP GMP
PQ: CPP GMP
!
!
Qualification
May 2015, page 22
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 virus-
inactivation 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
… ….
How to perform DQ for layouts? Checklists prepared on the basis of the URS (challenged and confirmed by RA!) Have requirements indicated precisely!
May 2015, page 23
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.
After DQ ! Change Control
Routine Production
Engineering
Manufac- turing
Delivery/ Installation
Commiss-ioning
Test Runs/ Start-up
Process Optimi-sation
DQ/FDS Re-Val. PV / CV OQ FAT URS PQ
Change Control / Requalification - Revalidation
IQ/SAT
Detail RA Basic RA
DQ = qualified status ! required Change Control
May 2015, page 24
GEP
GEP
DQ
GMP-CC
Project Execution Routine Use
GEP
GMP-CC
Maintaining the qualified state
Good Practices in Documentation Good Engineering Practice / GMP
After DQ ! Change Control
May 2015, page 25
" GMP-relevant requirements are defined in the specification phase
(before the equipment is ordered!) ! Unexpected GMP-problems in later qualification phases become unlikely. Economic Aspect!
" GMP-relevant requirements fixed in DQ-Protocols ! Preparation of IQ/ OQ/ PQ-protocols easy
“Disadvantage”: Much theoretical work at an early project phase!
Advantages provided by DQ
May 2015, page 26
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.
Contact: Pharma Consulting Walther Dr. Ingrid Walther Rosenweg 36 61381 Friedrichsdorf – Germany +49-(0)6172-958281 +49-(0)172 654 8834 www.consulting-walther.com [email protected]