The International Pharmaceutical Excipients Council& The Pharmaceutical Quality GroupThe Joint Good
Manufacturing
Practices Guide
For Pharmaceutical Excipients

Version 5
2022

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality Group

This document represents voluntary guidance for the excipient industry and the contents
should not be interpreted as regulatory requirements. Alternatives to the approaches in thisguide may be used to achieve an equivalent level of assurance for excipient quality.
This guide was created to help companies understand current expectations on this topic and is
not intended for use by third party certification bodies to conduct audits or to certify
compliance with the guide.
The content of this guide cannot be reproduced without the written authorisation of the IPEC
Federation and PQG Management Bodies.

FOREWORDIPECThe International Pharmaceutical Excipients Council (IPEC) is an international industry
association formed by excipient manufacturers, distributors and users. At the current writing there
are regional pharmaceutical excipient industry associations located in the Americas, Europe,
Japan, China, and India. IPEC’s objective is to contribute to the international excipient standards
development and harmonization, provide information useful for new excipient development andintroduction, and offer best practice and guidance concerning excipient manufacture.
IPEC has three major stakeholder groups:
1. excipient manufacturers and distributors, defined as suppliers in IPEC documents,
2. pharmaceutical manufacturers, defined as users in this document, and3. public health and regulatory authorities.

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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PQG
The PQG was formed in 1977 to promote development of a consistent approach topharmaceutical quality and good manufacturing practice. The group has since expanded, and in1990 the PQG published three codes of practice to cover pharmaceutical raw materials, printed
and contact packaging materials. In 1995 the codes were revised and were integrated with ISO
9002:1994. The code for raw materials was revised and reissued as PS 9100:2002
Pharmaceutical excipients, an application standard and GMP guide for pharmaceutical
excipients.
For further information, visit www.pqg.org.

This guide is intended to be voluntary, to indicate best practice, and to be globally applicable.
However, it should be recognized that the rules and regulations applying to excipients will varyfrom region to region and country to country. In addition, the rules and regulations are continually
evolving. It is the responsibility of the reader to review the latest version of the applicableregulatory guidance; however, the version referenced in the guide will be based on the version
available at the time the guide was published.
In this guide, pharmaceutical excipient(s) will be referred as excipient(s). This guide may be
applied to veterinary medicines, as appropriate with reference to specific veterinary guidance andregulations.
Throughout the guide, justification implies that a decision is made based on a scientific, quality
and/or regulatory considerations.

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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Table of Contents
FOREWORD ................................................................................................................... 1
TABLE OF CONTENTS................................................................................................. 3
PART 1 - IPEC-PQG GMP GUIDE ............................................................................... 15
1

Introduction..................................................................................................... 15

1.1

Purpose and scope ...................................................................................................15

1.2

Principles adopted ....................................................................................................15

1.2.1

The guide and its use ................................................................................................15

1.2.2

Application.................................................................................................................16

1.2.3

Quality System standard ..........................................................................................16

1.3

Layout and definitions ..............................................................................................16

1.3.1

Layout ........................................................................................................................16

1.3.2

Definitions..................................................................................................................17

2

General Guidance ........................................................................................... 18

3

Excipient GMP implementation ..................................................................... 18

4

Context of the organization ........................................................................... 19

4.1

Understanding the organization and its context .....................................................19

4.2

Understanding the needs and expectations of interested parties .........................19

4.3

Determining the scope of the Quality Management System ..................................19

4.4

Quality Management System and its processes .....................................................20

5

Leadership ...................................................................................................... 21

5.1

Leadership and commitment ....................................................................................21

5.1.1

General .......................................................................................................................21

5.1.2

Customer focus .........................................................................................................21

5.2

Quality policy .............................................................................................................21

5.2.1

Establishing the quality policy .................................................................................21

5.2.2

Communicating the quality policy ...........................................................................22

5.3

Organizational roles, responsibilities, and authorities ...........................................22

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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6

Planning .......................................................................................................... 24

6.1

Actions to address risks and opportunities in the Quality Management System .24

6.1.1

Risk Assessment.......................................................................................................24

6.1.2

Preventive action and continual improvement........................................................24

6.2

Quality and GMP objectives and planning to achieve them ...................................24

6.3

Planning of changes .................................................................................................25

7

Support ............................................................................................................ 25

7.1

Resources ..................................................................................................................25

7.1.1

General .......................................................................................................................25

7.1.2

People ........................................................................................................................26

7.1.3

Infrastructure .............................................................................................................26

7.1.3.1 Buildings and facilities .................................................................................................26
7.1.3.2 Equipment ...................................................................................................................27
7.1.3.3 Utilities ........................................................................................................................28
7.1.3.4 Water ..........................................................................................................................28
7.1.3.5 Recycled or recovered materials .................................................................................29
7.1.4

Environment for the operation of processes...........................................................29

7.1.4.1 Environmental air handling ..........................................................................................30
7.1.4.2 Controlled environment ...............................................................................................30
7.1.4.3 Clean and sanitary conditions......................................................................................30
7.1.4.4 Pest control .................................................................................................................31
7.1.4.5 Personnel hygiene.......................................................................................................31
7.1.4.6 Lighting .......................................................................................................................32
7.1.4.7 Drainage .....................................................................................................................32
7.1.4.8 Waste ..........................................................................................................................32
7.1.5

Monitoring and measuring resources......................................................................32

7.1.5.1 General .......................................................................................................................32
7.1.5.2 Measurement traceability ............................................................................................33
7.1.6

Organizational knowledge ........................................................................................33

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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7.2

Competence...............................................................................................................33

7.3

Awareness .................................................................................................................33

7.4

Communication .........................................................................................................34

7.5

Documented information ..........................................................................................35

7.5.1

General documentation requirements .....................................................................35

7.5.2

Creating and updating ..............................................................................................36

7.5.3

Control of documented information.........................................................................37

8

Operation......................................................................................................... 37

8.1

Operational planning and control ............................................................................37

8.2

Requirements for excipients and GMP services .....................................................38

8.2.1

Customer communication ........................................................................................38

8.2.2

Determining the requirements for excipients and GMP services ..........................39

8.2.3

Review of the requirements for excipients and GMP services ..............................39

8.2.4

Changes to requirements for excipients and GMP services ..................................39

8.3

Design and development of excipients and GMP services ....................................39

8.3.1

General .......................................................................................................................39

8.3.2

Design and development planning ..........................................................................39

8.3.3

Design and development inputs...............................................................................40

8.3.4

Design and development controls ...........................................................................40

8.3.5

Design and development outputs ............................................................................41

8.3.6

Design and development changes ...........................................................................41

8.4

Control of externally provided quality critical processes, services and materials ..
....................................................................................................................................42

8.4.1

General .......................................................................................................................428.4.2

Type and extent of control ........................................................................................42

8.4.2.1 Control of externally-provided processes and services ................................................42
8.4.2.2 Control of externally-provided materials ......................................................................42
8.4.3

Information for external providers ...........................................................................43

8.5

Production and GMP service provision ...................................................................44

Copyright © 2022 The International Pharmaceutical Excipients Council
Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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8.5.1

Control of production and GMP service provision .................................................44

8.5.1.1 Instructions and records ..............................................................................................44
8.5.1.2 Equipment cleaning .....................................................................................................45
8.5.1.3 Recovery and reuse of materials .................................................................................46
8.5.1.4 Blending of excipients .................................................................................................46
8.5.1.5 Co-processing of excipients ........................................................................................46
8.5.1.6 In-process control ........................................................................................................46
8.5.1.7 Packaging and labeling of excipients ...........................................................................47
8.5.1.8 Validation for production and GMP service provision ...................................................47
8.5.2

Identification and traceability ...................................................................................48

8.5.2.1 Traceability ..................................................................................................................48
8.5.2.2 Inspection and test status ............................................................................................48
8.5.2.3 Labels .........................................................................................................................48
8.5.3

Property belonging to customers or external providers ........................................49

8.5.4

Preservation ..............................................................................................................49

8.5.4.1 Handling, storage, and preservation ............................................................................49
8.5.4.2 Packaging ...................................................................................................................49
8.5.4.3 Delivery and distribution ..............................................................................................50
8.5.5

Post-delivery activities..............................................................................................50

8.5.6

Control of changes....................................................................................................51

8.6

Release of excipients and GMP services.................................................................51

8.6.1

Monitoring and measurement ..................................................................................51

8.6.2

Laboratory controls ..................................................................................................51

8.6.3

Finished excipient testing and release ....................................................................53

8.6.4

Out-of-specification test results ...............................................................................53

8.6.5

Retained samples ......................................................................................................54

8.6.6

Certificates of analysis .............................................................................................54

8.6.7

Impurities ...................................................................................................................54

8.6.8

Stability ......................................................................................................................55

Copyright © 2022 The International Pharmaceutical Excipients Council
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Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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8.6.9Expiry date or re-evaluation period..........................................................................55

8.7

Control of nonconforming outputs ..........................................................................55

8.7.1

Control of nonconforming intermediates and finished excipients ........................55

8.7.1.1 Reprocessing ..............................................................................................................56
8.7.1.2 Reworking ...................................................................................................................56
8.7.1.3 Returned excipients.....................................................................................................56
8.7.2

Control of nonconforming GMP services ................................................................57

8.7.3

Customer complaint handling ..................................................................................58

8.7.4

Recall / Retrieval........................................................................................................58

9

Performance evaluation ................................................................................. 59

9.1

Monitoring, measurement, analysis and evaluation ...............................................59

9.1.1

General .......................................................................................................................59

9.1.2

Customer satisfaction ...............................................................................................59

9.1.3

Analysis and evaluation ............................................................................................59

9.2

Internal audit..............................................................................................................60

9.3

Management review ..................................................................................................60

9.3.1

General .......................................................................................................................60

9.3.2

Management review inputs .......................................................................................61

9.3.3

Management review outputs ....................................................................................61

10

Improvement ................................................................................................... 62

10.1

General .......................................................................................................................62

10.2

Nonconformity and corrective action ......................................................................62

10.3

Continual improvement ............................................................................................63

11

References ...................................................................................................... 64

PART 2 - IPEC-PQG GMP GUIDE AND NOTES ......................................................... 68
1

Introduction..................................................................................................... 68

1.1

Purpose and scope ...................................................................................................68

1.2

Principles adopted ....................................................................................................68

1.2.1

The guide and its use ................................................................................................68

Copyright © 2022 The International Pharmaceutical Excipients Council
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Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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1.2.2

Application.................................................................................................................69

1.2.3

Quality System standard ..........................................................................................69

1.3

Layout and definitions ..............................................................................................69

1.3.1

Layout ........................................................................................................................69

1.3.2

Definitions..................................................................................................................70

2

General Guidance ........................................................................................... 72

3

Excipient GMP implementation ..................................................................... 72

4

Context of the organization ........................................................................... 73

4.1

Understanding the organization and its context .....................................................73

4.2

Understanding the needs and expectations of interested parties .........................75

4.3

Determining the scope of the Quality Management System ..................................76

4.4

Quality Management System and its processes .....................................................77

5

Leadership ...................................................................................................... 79

5.1

Leadership and commitment ....................................................................................79

5.1.1

General .......................................................................................................................79

5.1.2

Customer focus .........................................................................................................80

5.2

Quality policy .............................................................................................................80

5.2.1

Establishing the quality policy .................................................................................80

5.2.2

Communicating the quality policy ...........................................................................81

5.3

Organizational roles, responsibilities, and authorities ...........................................81

6

Planning .......................................................................................................... 84

6.1

Actions to address risks and opportunities in the Quality Management System .84

6.1.1

Risk Assessment.......................................................................................................84

6.1.2

Preventive action and continual improvement........................................................85

6.2

Quality and GMP objectives and planning to achieve them ...................................86

6.3

Planning of changes .................................................................................................877

Support ............................................................................................................ 87

7.1

Resources ..................................................................................................................87

7.1.1

General .......................................................................................................................87

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Copyright © 2022 Pharmaceutical Quality GroupThe International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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7.1.2People ........................................................................................................................87

7.1.3

Infrastructure .............................................................................................................88

7.1.3.1 Buildings and facilities .................................................................................................88
7.1.3.2 Equipment ...................................................................................................................89
7.1.3.3 Utilities ........................................................................................................................92
7.1.3.4 Water ..........................................................................................................................92
7.1.3.5 Recycled or recovered materials .................................................................................94
7.1.4

Environment for the operation of processes...........................................................94

7.1.4.1 Environmental air handling ..........................................................................................95
7.1.4.2 Controlled environment ...............................................................................................95
7.1.4.3 Clean and sanitary conditions......................................................................................96
7.1.4.4 Pest control .................................................................................................................97
7.1.4.5 Personnel hygiene.......................................................................................................98
7.1.4.6 Lighting .......................................................................................................................99
7.1.4.7 Drainage .....................................................................................................................99
7.1.4.8 Waste ..........................................................................................................................99
7.1.5

Monitoring and measuring resources....................................................................100

7.1.5.1 General .....................................................................................................................100
7.1.5.2 Measurement traceability ..........................................................................................101
7.1.6

Organizational knowledge ......................................................................................101

7.2

Competence.............................................................................................................102

7.3

Awareness ...............................................................................................................103

7.4

Communication .......................................................................................................104

7.5

Documented information ........................................................................................105

7.5.1

General documentation requirements ...................................................................105

7.5.2

Creating and updating ............................................................................................109

7.5.3

Control of documented information.......................................................................109

8

Operation....................................................................................................... 111

8.1

Operational planning and control ..........................................................................111

Copyright © 2022 The International Pharmaceutical Excipients Council
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Rue Marie de Bourgogne 52 - 1000, Brussels, Belgium
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8.2

Requirements for excipients and GMP services ...................................................111

8.2.1

Customer communication ......................................................................................111

8.2.2

Determining the requirements for excipients and GMP services ........................112

8.2.3

Review of the requirements for excipients and GMP services ............................112

8.2.4

Changes to requirements for excipients and GMP services ................................113

8.3

Design and development of excipients and GMP services ..................................113

8.3.1

General .....................................................................................................................113

8.3.2

Design and development planning ........................................................................113

8.3.3

Design and development inputs.............................................................................114

8.3.4

Design and development controls .........................................................................115

8.3.5

Design and development outputs ..........................................................................115

8.3.6

Design and development changes .........................................................................116

8.4

Control of externally provided quality critical processes, services and materials ..
..................................................................................................................................117

8.4.1

General .....................................................................................................................117

8.4.2

Type and extent of control ......................................................................................117

8.4.2.1 Control of externally-provided processes and services ..............................................118
8.4.2.2 Control of externally-provided materials ....................................................................118
8.4.3

Information for external providers .........................................................................119

8.5

Production and GMP service provision .................................................................121

8.5.1

Control of production and GMP service provision ...............................................121

8.5.1.1 Instructions and records ............................................................................................121
8.5.1.2 Equipment cleaning ...................................................................................................123
8.5.1.3 Recovery and reuse of materials ...............................................................................123
8.5.1.4 Blending of excipients ...............................................................................................124
8.5.1.5 Co-processing of excipients ......................................................................................124
8.5.1.6 In-process control ......................................................................................................125
8.5.1.7 Packaging and labeling of excipients .........................................................................125
8.5.1.8 Validation for production and GMP service provision .................................................126

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The International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
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VAT: BE 0823931361 - IBAN: BE73363068125160 - RPM Brussels Capital Region

8.5.2

Identification and traceability .................................................................................127

8.5.2.1 Traceability ................................................................................................................127
8.5.2.2 Inspection and test status ..........................................................................................128
8.5.2.3 Labels .......................................................................................................................128
8.5.3

Property belonging to customers or external providers ......................................128

8.5.4

Preservation ............................................................................................................129

8.5.4.1 Handling, storage, and preservation ..........................................................................129
8.5.4.2 Packaging .................................................................................................................130
8.5.4.3 Delivery and distribution ............................................................................................130
8.5.5

Post-delivery activities............................................................................................131

8.5.6

Control of changes..................................................................................................132

8.6

Release of excipients and GMP services...............................................................132

8.6.1

Monitoring and measurement ................................................................................132

8.6.2

Laboratory controls ................................................................................................133

8.6.3

Finished excipient testing and release ..................................................................136

8.6.4

Out-of-specification test results .............................................................................136

8.6.5

Retained samples ....................................................................................................137

8.6.6

Certificates of analysis ...........................................................................................137

8.6.7

Impurities .................................................................................................................137

8.6.8

Stability ....................................................................................................................138

8.6.9

Expiry date or re-evaluation period........................................................................138

8.7

Control of nonconforming outputs ........................................................................139

8.7.1

Control of nonconforming intermediates and finished excipients ......................139

8.7.1.1 Reprocessing ............................................................................................................140
8.7.1.2 Reworking .................................................................................................................140
8.7.1.3 Returned excipients...................................................................................................141
8.7.2

Control of nonconforming GMP services ..............................................................141

8.7.3

Customer complaint handling ................................................................................142

8.7.4

Recall / Retrieval......................................................................................................142

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VAT: BE 0823931361 - IBAN: BE73363068125160 - RPM Brussels Capital Region

9Performance evaluation ............................................................................... 143

9.1

Monitoring, measurement, analysis and evaluation .............................................143

9.1.1

General .....................................................................................................................143

9.1.2

Customer satisfaction .............................................................................................143

9.1.3

Analysis and evaluation ..........................................................................................144

9.2

Internal audit............................................................................................................144

9.3

Management review ................................................................................................146

9.3.1

General .....................................................................................................................146

9.3.2

Management review inputs .....................................................................................146

9.3.3

Management review outputs ..................................................................................147

10

Improvement ................................................................................................. 147

10.1

General .....................................................................................................................147

10.2

Nonconformity and corrective action ....................................................................148

10.3

Continual improvement ..........................................................................................149

11

References .................................................................................................... 150

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The International Pharmaceutical Excipients Council – Federation (IPEC Federation) asbl
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VAT: BE 0823931361 - IBAN: BE73363068125160 - RPM Brussels Capital Region

ACKNOWLEDGEMENTS
This guide was developed by representatives from International Pharmaceutical Excipients
Council (IPEC) and the Pharmaceutical Quality Group (PQG) member companies.
IPEC is an industry association whose members consist of excipient manufacturers, distributors,
and users.
IPEC and PQG greatly appreciate the many hours devoted by the core team of individuals andother contributors listed below, to make this guide available to IPEC members and the broader
excipient community. Equally, IPEC and PQG extend their thanks to the employers of those same
contributors who provide the necessary time and resources, without which, this guide would not
be possible.
The company representatives who worked on this guide are listed below:

List of Contributors from IPEC-Americas
William Dale Carter*, Evonik
George Collins, Vanderbilt Chemicals LLC
Ann Gulau, IFF

List of Contributors from IPEC Europe
Jeffrey Brambora, Consultant
Roberto Mastrantonio, Eli Lilly
Astrid Stockrahm-Uhling*+, DFE Pharma
Beverley Stout, GSK

List of Contributors from PQG
Ian McKeown, PQ Silicas* co-chair+ task force team leader

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VAT: BE 0823931361 - IBAN: BE73363068125160 - RPM Brussels Capital Region