GMP Equipment Design Guide

Table of contents

Table of contents ........................................................................................................................ 2

1. Introduction: What does GMP-compliant design of equipment mean?........................................... 7
2. Overview: General GMP rules, standards, interest groups and state of the art ............................. 10
3. Risk analysis: the key to pharmaceutical success? .................................................................... 13
4. Demonstration of evidence: URS, FDS -> GMP design -> qualification........................................ 15
5. Material selection for hygiene-critical areas .............................................................................. 17
5.1 Material selection ............................................................................................................. 17
5.2 Surfaces .......................................................................................................................... 18
5.3 Considerations on material selection for the process environment......................................... 19
5.4 Conclusion: a risk-based approach for the selection of suitable materials .............................. 19
5.5 References ...................................................................................................................... 20
6. Process contact surface requirements: surface specifications and surface treatments .................. 21
6.1 Surface qualities/specifications .......................................................................................... 21
6.2 Surface treatment methods ............................................................................................... 24
6.2.1 Mechanical surface treatment methods ........................................................................... 24
6.2.2 Chemical surface treatment ............................................................................................ 25
6.2.3 Electrochemical surface treatment .................................................................................. 27
6.3 Summary......................................................................................................................... 29
6.4 Definitions/glossary .......................................................................................................... 30
6.5 References ...................................................................................................................... 30
7. Hygienic design - basic aspects ............................................................................................... 33
7. 1 Equipment-specific definition of the hygiene-critical area .................................................... 34
7.2 Aspects of hygienic design – closed equipment ................................................................... 34
7.2.1 Complete drainability ..................................................................................................... 34
7.2.2 Permanent pipe connections ........................................................................................... 36
7.2.3 Detachable connections ................................................................................................. 36
7.3 Aspects of hygienic design – open equipment ..................................................................... 36
7.3.1 Accessibility .................................................................................................................. 37
7.3.2 Removable elements ..................................................................................................... 37
7.3.3 Transparency ................................................................................................................ 37
7.3.4 Screw joints .................................................................................................................. 38
7.3.5 Inner corners and angles ............................................................................................... 38
7.3.6 Horizontal surfaces ........................................................................................................ 38

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GMP Equipment Design Guide

7.4 Summary......................................................................................................................... 39
7.5 References ...................................................................................................................... 39
8. Pipework and fittings, connections, welding & seam control ...................................................... 41
8.1 Pipework and fittings ........................................................................................................ 41
8.1.1 Dead legs - construction of pipe systems ......................................................................... 42
8.1.2 Detachable connections of pipe systems .......................................................................... 44
8.2 Welding technology .......................................................................................................... 48
8.3 Definitions / glossary ........................................................................................................ 54
9. Requirements for the process environment: the clean room ...................................................... 55
9.1. Selection and procurement............................................................................................... 58
9.2 Wall and ceiling systems ................................................................................................... 59
9.2.1 Wall panelling, coating ................................................................................................... 61
9.2.2 Wall systems ................................................................................................................. 62
9.2.3 Ceiling systems ............................................................................................................. 64
9.3 Doors and windows .......................................................................................................... 66
9.4 Floor systems .................................................................................................................. 72
9.4.1 Construction alternatives ................................................................................................ 73
9.4.2 Approval of floors .......................................................................................................... 77
9.4.3 Critical clean room interfaces .......................................................................................... 78
9.5 Areas of application of the components for different cleanliness classes ................................ 79
9.6 Definitions / glossary ........................................................................................................ 82
10. Electrical engineering, measurement and control technology in the GMP-regulated environment . 83
10.1 Technical design............................................................................................................. 83
10.2 Selection of the appropriate measurement procedure ........................................................ 85
10.3 Maintenance and calibration ............................................................................................ 86
10.4 Definitions / glossary ...................................................................................................... 87
10.5 References .................................................................................................................... 88
11. Requirements for automation and control systems .................................................................. 89
11.1 Qualification or validation ................................................................................................ 89
11.2 Delimitation of the subsystems ........................................................................................ 90
11.3 Special feature - configuration management ..................................................................... 91
11.4 Data integrity ................................................................................................................. 91
11.5 Integration of FAT and SAT in the validation ..................................................................... 93
11.6 Definitions / glossary ...................................................................................................... 93
11.6 References .................................................................................................................... 94
12. Documentation in the lifecycle of GMP equipment ................................................................... 95
12.1 Documentation in basic engineering ................................................................................. 95
12.2 Documentation in detail engineering & implementation...................................................... 96

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GMP Equipment Design Guide

12.3 Important documents for qualification .............................................................................. 97

12.4 Operating documentation ................................................................................................ 98
12.5 Material certificates ........................................................................................................ 99
12.5.1 Material certificates for metallic materials ...................................................................... 99
12.5.2 Material certificates for product or media-contacting plastics (e.g. seals/gaskets) .............. 99
12.6 Formal aspects ............................................................................................................. 100
12.7 Definitions/glossary ...................................................................................................... 101
12.8 References .................................................................................................................. 101
13. Requirements on quality assurance systems for equipment suppliers ...................................... 102
13.1 Quality management systems: DIN ISO 9001 as a basis .................................................. 102
13.2 Quality management systems: overlap with GMP ............................................................ 103
13.3 Qualification and validation at the equipment supplier ..................................................... 104
13.4 Further supplier quality systems .................................................................................... 105
13.5 Documentation............................................................................................................. 106
13.6 Production conditions ................................................................................................... 107
13.7 Differences between suppliers and pharmaceutical manufacturers .................................... 108
13.8 Definitions ................................................................................................................... 108
13.9 References .................................................................................................................. 109

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GMP Equipment Design Guide

Introduction
There are numerous pharmaceutical manufacturing processes, ranging from dry granulation and
tableting to fermentation or sterile filling. Adding manufacturing processes from the classical
(chemical) production of active pharmaceutical ingredients increases their number considerably. To
some extent, however, pharmaceutical requirements are also observed when producing medical
devices such as implants. The equipment used for these processes is as varied as the processes
themselves. The product itself can place multiple requirements on the production equipment, too. For
the design of equipment, it makes a big difference whether the product to be produced needs to be
sterile or not, or whether it is a highly effective product. In the latter case, not only do GMP design
criteria have to be observed, but also requirements for personal protection. A product or intermediate
may, however, also be sensitive to oxygen or moisture. Obviously, all this affects the design of
equipment. There might also be the rare case that the requirements of the authorities are not the
same in different countries. The production method for WFI (water for injection) for example, was
regulated differently in Europe than in the USA or in Japan until recently. In Europe, production of
WFI was limited to distillation. This means that systems producing WFI by means of reverse osmosis
would not have been GMP-compliant in Europe.

Consequently, this guidance cannot illustrate the requirements for every possible type of production
equipment. Moreover, there are books, seminars taking up whole days and even academic subjects
for each individual chapter. The purpose of this text is rather to illustrate the generally applicable
requirements for the design of equipment and to explain how the connection between design and the
statement “produced in compliance with GMP” can be made. To this end, the guidance contains
numerous references and points of contact, a sort of a road map, that offer detailed information on
the requirements or ways of proceeding for individual cases.

This guide was developed by a task force that included experts in pharmaceutical technology and
engineering. The Task Force initially developed a document in German and it was first published by
CONCEPT HEIDELBERG. The GMP-Equipment Guide is an English translation of the Guideline
developed by this Task Force.

All references to “he”, “him” or ”his“ should be read as ”she“/ ”her“ respectively “they” / “them” or “their” where appropriate.

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GMP Equipment Design Guide

GMP Equipment Design Guide

Authors
Selection of Material for Hygiene-critical Areas
&
Hygienic Design - Basic Aspects
Markus Keller, Fraunhofer Institute for Manufacturing Engineering and Automation IPA, Clean Room
Manufacturing and Microfabrication Department, Stuttgart. markus.keller@ipa.fraunhofer.de

Requirements for Surfaces: Surface Qualities and Surface Treatments

Dr Jan Rau; Dockweiler AG, j.rau@dockweiler.com
Pipework and Fittings; Detachable and Undetachable Connections including Welding
Markus Multhauf; Pharma-Process Engineering Multhauf; multhauf@engineer.com
Requirements for the Process Environment: The Clean Room
Nikolaus Ferstl; Engineering Firm for Building and Clean Room Technology; n.ferstl@t-online.de
Electrical, Instrumentation and Control Engineering (EI&C) (in the GMP-regulated
Environment)
Gerhard Kinzinger; gempex GmbH; gerhard.kinzinger@gempex.com
Requirements for Automation and Controls
Dr Georg Schwarz; gempex GmbH; georg.schwarz@gempex.com
Documentation in the LifeCycle of GMP Equipment
Jörg Koppenhöfer; gempex GmbH; joerg.koppenhoefer@gempex.com, Ivonne Leutert, Michael
Fiand – also gempex GmbH
Required Quality Assurance Systems of the Equipment Supplier
Dr Georg Sindelar, msg industry advisors ag; georg.sindelar@msg-advisors.com
As well as Dr Robert Eicher, Concept Heidelberg, eicher@concept-heidelberg.de

Version
Version 1.0 – June 2022

Technical Review
Gert Moelgaard, Ulrich Bieber, Dr. Friedrich Elstner, Wolfgang Schmitt, Markus Multhauf, Georg
Sindelar

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Attn Mr J. Ruland
Hebelstr. 7
68161 Mannheim
Germany

If you have any comments regarding ECA or this Guide please contact us by E-Mail at
info@gmp-compliance.org.

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