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!

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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

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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

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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

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User Requirement Specification – a new requirement!

Check the defined requirements by an RA

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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!

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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

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"  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 iw@consulting-walther.com