Pharmaceutical Packaging PDF

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PS 9000:2011
Pharmaceutical packaging materials for
medicinal products, with reference to
Good Manufacturing Practice (GMP)
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Foreword
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Acknowledgements
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2 Normative reference
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7 Product realization
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Measurement, analysis
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and improvement been added which can be used rather than scrolling.
Guidance on risk
A
management Internal links and the return button
Guidance on verification Within the document you will come across many internal links, for
B
and validation requirements example (see 3.2). Clicking on any of these will take you to the
C Barcodes specific section. When you are finished, you can click on the return
button at any time, taking you back to the page you originally came
D Cleanrooms from.
E Drug Master Files (DMF)

Supplier Certification
F
Scheme
G Bibliography
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© 2011 The Chartered Quality Institute - Ver 1.0 2011 2
Contents
Home
Home p01 5.5.5 Internal communication p26
Contents
How to use this document p02 5.6 Management review p27
Foreword Contents p03 5.6.1 General p27
Acknowledgements Foreword p06 5.6.2 Review input p27
0 Introduction Acknowledgements p07 5.6.3 Review output p27
0 Introduction p08 6 Resource management p28
1 Scope 0.1 General p08 6.1 Provision of resources p28
0.2 Relationship with ISO 9001:2008 and ISO 15378:2006 p09 6.2 Human resources p28
2 Normative reference 1 Scope p10 6.2.1 General p28
1.1 General p10 6.2.2 Competence, awareness and training p28
3 Terms and definitions
1.2 Application p10 6.3 Infrastructure p29
4
Quality management 2 Normative reference p11 6.4 Work environment p30
system
3 Terms and definitions p12 6.4.1 Environmental conditions p30
5 Management responsibility 4 Quality management system p22 6.4.1.1 Minimum environmental conditions p30
4.1 General requirements p22 6.4.2 Classification of clean areas/cleanrooms p30
4.2 Documentation requirements p22 6.4.3 Risk control of contamination p31
4.2.1 General p22 6.4.3.1 Hygiene and security p31
4.2.2 Quality manual p22 6.4.4 Pest control p31
8
Measurement, analysis 4.2.3 Control of documents p22 6.4.5 Materials and utilities p31
and improvement
4.2.3.1 System administration p23 6.4.5.1 General p31
Guidance on risk
A
management 4.2.4 Control of records p23 6.4.5.2 General requirements for primary packaging materials p31
Guidance on verification 5 Management responsibility p25 6.5 Maintenance and cleaning activities p32
B 5.1 Management commitment p25 7 Product realization p33
and validation requirements
C Barcodes
5.2 Customer focus p25 7.1 Planning of product realization p33
5.2.1 Customer audits p25 7.2 Customer-related processes p33
D Cleanrooms 5.3 Quality policy p25 7.2.1 Determination of requirements related to the product p33
5.4 Planning p25 7.2.1.1 Customer product component codes p33
E Drug Master Files (DMF) 5.4.1 Quality objectives p25 7.2.1.2 Specifications p34
Supplier Certification 5.4.2 Quality management system planning p25 7.2.1.3 Additional requirements p34
F
Scheme 5.5 Responsibility, authority and communication p26 7.2.2 Review of requirements related to the product p34
G Bibliography
5.5.1 Responsibility and authority p26 7.2.3 Customer communication p34
5.5.2 Management representative p26 7.2.3.1 Complaints p35
5.5.3 Quality unit authority p26 7.2.3.2 Supply agreements, quality agreements and documentation p35
5.5.4 Quality unit responsibility p26 7.3 Design and development p36
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Contents
Home
7.3.1 Design and development planning p36 d) Digital printing p45
Contents
7.3.1.1 Material use-by/requalification date p37 e) Gang printing p45
Foreword 7.3.1.2 Process Analytical Technology (PAT) p37 7.5.1.12 Printed materials p45
Acknowledgements 7.3.2 Design and development inputs p37 a) Leaflets p45
0 Introduction 7.3.2.1 Marketing Authorisation p38 b) Reel fed materials (general) p45
7.3.3 Design and development outputs p38 c) Reel fed self-adhesive labels p45
1 Scope 7.3.4 Design and development review p38 d) Combination products p45
7.3.5 Design and development verification p38 7.5.1.13 Braille p46
2 Normative reference 7.3.6 Design and development validation p39 7.5.1.14 Change control p46
7.3.7 Control of design and development changes p39 7.5.2 Validation of processes for production and service provision p47
7.3.7.1 Notification p39 7.5.2.1 Validation of software provision p48
4
Quality management 7.3.7.2 Design change p39 7.5.2.2 Revalidation of processes for production and service provision p48
system
7.4 Purchasing p39 7.5.2.3 Verification methods/equipment p48
5 Management responsibility 7.4.1 Purchasing process p39 7.5.3 Identification and traceability p49
7.4.1.1 Control of supply chain p40 7.5.4 Customer property p50
7.4.2 Purchasing information p40 7.5.5 Preservation of product p50
7.4.3 Verification of purchased product p40 7.5.5.1 Batched production and stock holding p51
7.4.4 Supplier data verification p41 7.6 Control of monitoring and measuring devices p51
8
Measurement, analysis 7.5 Production and service provision p41 8 Measurement, analysis and improvement p52
and improvement
7.5.1 Control of production and service provision p41 8.1 General p52
Guidance on risk
A
management 7.5.1.1 Cleanliness of product and contamination controls p41 8.2 Monitoring and measurement p52
Guidance on verification 7.5.1.2 General p41 8.2.1 Customer satisfaction p52
B 7.5.1.3 Particular requirements for sterile primary packaging materials p42 8.2.2 Internal audit p52
C Barcodes
7.5.1.4 Segregation controls p42 8.2.3 Monitoring and measurement of processes p52
7.5.1.5 Line-clearance p42 8.2.3.1 Control of processing aids p53
D Cleanrooms 7.5.1.6 Changeover systems p42 8.2.3.2 Controlled extraction studies p53
7.5.1.7 Quarantine and destruction p42 8.2.3.3 Control of extractables p53
E Drug Master Files (DMF) 7.5.1.8 Waste material p43 8.2.4 Monitoring and measurement of product p54
Supplier Certification 7.5.1.9 Origination/artwork p43 8.2.4.1 Investigations of OSS results p54
F
Scheme 7.5.1.10 Product security p43 8.2.4.2 Incomming inspection and testing p54
G Bibliography
7.5.1.11 Print related processes p44 8.2.4.3 In-process controls p54
a) Print impression media p44 8.2.4.4 Final inspection p55
b) Plate management p44 8.2.4.5 Retained samples p55
c) Print machine set-up (initial make-ready) p44 8.2.4.6 Product release p55
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Contents
Home
8.2.4.7 Characterisation and functionality testing p55 Annex D (normative) p69
Contents
8.3 Control of nonconforming product p55 Cleanrooms
Foreword 8.4 Analysis of data p56 D.1 Standard cleanroom conditions p69
Acknowledgements 8.5 Improvement p56 D.2 Enhanced cleanroom conditions p69
0 Introduction 8.5.1 Continual improvement p56 Annex E (informative) p71
8.5.2 Corrective action p57 Drug Master Files (DMF)
1 Scope 8.5.3 Preventive action p57 E.1 Drug Master Files (DMFs) p71
Annex A (informative) p58 E.2 Types of DMFs p71
2 Normative reference Guidance on risk management E.3 Benefits p71
Annex B (informative) p60 E.4 Requirements for DMF holders p72
Guidance on verification and validation requirements E.5 Subcontracting p72
4
Quality management B.1 The key stages of validation p60 E.6 Letters of Authorisation for FDA to refer to DMFs p72
system
B.2 Alternative approaches to validation p60 Annex F (normative) p73
5 Management responsibility Annex C (informative) p61 PS 9000:2011 CQI/PQG Pharmaceutical Supplier
Barcodes Certification Scheme
C.1 Barcode types p61 F.1 Requirements for CQI/PQG certified supplier status p73
C.1.1 General p61 F.1.1 The organization p73
C.2 Security codes p61 F.1.2 The International Register of Certificated Auditors (IRCA) p73
8
Measurement, analysis C.3 Barcode systems p61 F.1.3 The auditor p73
and improvement
C.3.1 Pharmacode p61 F.1.4 The accredited certification body p74
Guidance on risk
A
management C.3.2 Interleaved two of five (ITF) codes p61 F.2 PS 9000 Registration/certification requirements p74
Guidance on verification C.3.3 Code 39 (also described as Code 3 of 9) p61 F.2.1 The accredited certification body p74
B C.3.4 Code 128 p62 F.2.2 The CQI Pharmaceutical Quality Group (PQG) p74
C Barcodes
C.3.5 Crease codes p62 F.3 PS 9000 Third party certification audit timescales p75
C.3.6 Two-dimensional (2D) Matrix barcode p62 F.3.1 Surveillance and re-assessment p76
D Cleanrooms C.3.7 Alternative Two-dimensional barcodes p62 F.3.2 Multiple Site Certifications p76
C.3.8 Alternative security codes p63 F.3.3 Organizations with minimal PS 9000 activity p76
E Drug Master Files (DMF) C.4 Communication codes p63 F.3.4 Transition p76
Supplier Certification C.4.1 Global Standards 1 (GS 1) p63 F.3.5 Transition from PS 9000:2001 to PS 9000:2011 p76
F
Scheme C.4.2 Traded unit codes p63 Bibliography p77
G Bibliography
C.4.3 Other communication codes p63
C.4.4 Others p63
C.5 Barcode layout on products p65
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Foreword
Home
Contents
Foreword
The EU Guide to Good Manufacturing Practice (GMP) rightly This PQG Standard provides an important reference text to assist
Acknowledgements emphasizes the importance of pharmaceutical packaging medicinal product manufacturers and their suppliers in their
0 Introduction materials and in particular the importance of the relationship understanding of their respective responsibilities in producing
between supplier and customer. Key to this is a common and materials of the requisite quality, in order that the final product is
1 Scope shared understanding of the risks associated with the packaging fit for purpose. The PQG are to be commended for making this
operations at each site in order that risk mitigation plans can be Standard freely available to encourage its use. This will ultimately
2 Normative reference effectively adopted. Risk Management should be a key aspect in improve the quality of Pharmaceutical products by improving the
the supplier selection, approval and management process if the capability and suitability of the supply chain, thereby supporting the
3 Terms and definitions quality and continuity of supply of medicines and medical devices most important objective of Industry and Regulators alike, namely
is to be assured. PS 9000:2011 provides a common platform for the assurance of patient safety.
Quality management
4 the sharing of knowledge and practices across the diverse supply
system Gerald W Heddell
chain of the pharmaceutical industry.
5 Management responsibility Director, Inspection Enforcement & Standards Division
Each year the Medicines and Healthcare products Regulatory
Medicines and Healthcare products Regulatory Agency
6 Resource management Agency (MHRA) receives and investigates a number of reports of
quality defects concerning medicinal products leading to recalls.
7 Product realization A significant proportion of these, concern packaging errors, the
root cause investigations of which invariably involve all players
8
and improvement
throughout the supply chain. I consider that the clear differentiation
between ‘requirements’ and ‘guidance’ set out in this document
Guidance on risk
A
management serves to improve understanding and clarify the expectations of all
Guidance on verification
parties.
B
and validation requirements The strengthening of the supply chain in order to reduce the
C Barcodes threat from counterfeit medicines remains a high priority for
Regulators and Industry. The increasingly complex supply chain for
D Cleanrooms these items exposes the limitations of regulatory oversight by any
individual country. This serves to reinforce the need for everyone
E Drug Master Files (DMF) in the supply chain to understand their role and work to implement
and maintain a robust and comprehensive quality system. The
F
Scheme
Pharmaceutical Quality Group (PQG) Standard re-iterates the
importance of traceability and authentication of materials in order
G Bibliography to verify the provenance of the product. The inclusion of specific
references to electronic origination reinforces the importance of
control for each phase of the production process.
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Acknowledgements QA review panel

PS 9000:2011, A Standard for Pharmaceutical Packaging Materials Phil Butson, Esme Gibb, Tony Harper, Jill Jenkins, Colin
Home
Incorporating Good Manufacturing Practice (GMP), has been McEnaney, Lee Nagao, Linda Nield, Allan Whiston.
developed with the assistance and support of a wide variety of
people within the PQG and IPAC-RS, the supply industry and Consultation
Contents third party certification bodies. Acknowledgement is given for the
Foreword significant contribution of the following people: Consultations with industry suppliers, pharmaceutical companies
and other interested stakeholder organizations, delivered valuable
Acknowledgements
Joint steering committee PQG/IPAC-RS feedback at key maturity stages. This feedback was inspirational
0 Introduction and significantly assisted in the development of this Standard.
David Abraham, Mary Devlin Capizzi, Barbara Falco, Steve Moss,
Lee Nagao, Norman Randall. Other organizations consulted included IPAC-RS, PQG members
1 Scope
and Accredited Certification Bodies and the PQG would like to
Development team thank all those organizations and individuals who were consulted
and who responded with valuable feedback.
David Abraham (Project leader), Sacha Baldock, David Biggs,
3 Terms and definitions Richard Bream, Barbara Falco, Dee German, Esme Gibb, Tony Design facilitation
Quality management Harper, Afshin Hosseiny, Suzanne Ivory, Suzette Roan. Duncan
4
system Johnson, Colin McEnaney, Stuart Moodie, Linda Nield, Jeff Monk, This interactive PS 9000:2011 Standard has been designed
Paul Smith. and produced on behalf of PQG/IPAC-RS by Tag pac, a
5 Management responsibility Pharmaceutical Packaging Graphics Division of Tag Worldwide
In addition, the PQG would also like to extend its thanks to the and PS 9000 certified company.
6 Resource management many other individuals and organizations who have contributed to
the development of this document. Graphic Contributors
We would also like to express our thanks to individuals and
Measurement, analysis organizations who donated graphical images in support of this
8
and improvement document, with particular acknowledgement given to Lasercomb
Guidance on risk Dies Ltd , Nolato Cerbo and Stralfors.
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
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The format of this Standard is illustrated in Figure 1.

0. Introduction
Home
OINDP/
Increasing Requirement
Contents complex
Foreword materials
The structure of PS 9000:2011 has been aligned with
Acknowledgements Primary
ISO 15378:2006 so that title headings and numbering are Packaging
0 Introduction either similar or identical. This is intended to guide the user to Material
the corresponding part of the ISO standard, aiming to facilitate Secondary
compliance against the ISO requirements. Packaging
1 Scope
Materials
You can purchase a copy of BS EN ISO 15378:2006 via the
2 Normative reference BSI on-line shop or National Standards Bodies
Global QMS/GMP
3 Terms and definitions © 2011 The Chartered Quality Institute & IPAC-RS
Requirements
Quality management
All rights reserved.
4
system This document may be used in its entirety by freely downloading
5 Management responsibility from the websites of the Pharmaceutical Quality Group Figure 1. Standard format
www.pqg.org or the International Pharmaceutical Aerosol
6 Resource management Consortium on Regulation & Science www.ipacrs.com. Key Segment Application
The contents of this document must not be sold in whole or in part OINDP (orally inhaled Specific requirements applicable
7 Product realization in any form or by any means. Extracts from this document may and nasal drug products)/ to OINDP/complex materials
be quoted provided full acknowledgement of its source is given. Green
complex materials – specific
8
and improvement Any other usage of the content of this document requires written requirements (see 3.40 & 3.14)
permission from the Chartered Quality Institute or IPAC-RS. Primary Packaging Materials - Specific requirements for primary
Guidance on risk Blue
A specific requirements packaging materials.
management The Chartered Quality Institute, Chancery Exchange,
B
Guidance on verification 10 Furnival Street, London EC4A 1AB, UK www.thecqi.org Secondary Packaging Specific requirements applicable
and validation requirements Purple Materials to both secondary packaging and
C Barcodes
0.1 General printed primary materials
The safety of a patient using medicinal products is of paramount Global - QMS generic Applicable to all packaging
D Cleanrooms importance and so the pharmaceutical industry has specific requirements incorporating materials, in line with the products
Black
GMP – and services supplied
Good Manufacturing Practice (GMP) requirements, which provide
E Drug Master Files (DMF) applicable to all
assurance that the materials supplied to the pharmaceutical
Supplier Certification industry are of a suitable quality and fit for their intended use.
F
Scheme This Standard specifies GMP requirements and guidance within
G Bibliography a quality management system (QMS) for suppliers of packaging
materials and origination/artwork to the pharmaceutical industry
and has been developed through collaboration between the
pharmaceutical industry and its suppliers.
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• guidance is an integral part in this Standard and incorporated

using Italic font of the same colour coding as above
• guidance in Blue is applicable to both primary and OINDP/
Home Complex material supply
How to use this document • additional Guidance in Green is specific for OINDP/Complex
Contents material supply
Foreword
• primary printed materials needs to consider both Blue and Purple
• non-printed, secondary materials (e.g. white cartons for clinical)
Acknowledgements
need to consider the requirements of secondary / Purple with
0 Introduction appropriate exclusions for print
1 Scope
0.2 Relationship with ISO 9001:2008 and
ISO 15378:2006
2 Normative reference While PS 9000:2011 is a stand-alone Standard, it is essentially
based on ISO 9001:2008 and ISO 15378:2006. However the exact
3 Terms and definitions wording of these Standards has not been included in accordance
Quality management with copyright restrictions. Additional good manufacturing practices
4
system have been included.
5 Management responsibility
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
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Where requirements do not apply to an organization’s management

1. Scope system, exclusions can be claimed and shall be limited to
Clause 7 or the category of material supplied. These exclusions
Home do not absolve the organization from its responsibility to provide
How to use this document packaging materials that fully comply with the customer’s
Contents requirements and applicable statutory and regulatory requirements.
Foreword Where an organization claims exclusions, they shall be supported
1.1 General by documented justification approved by senior management.
Acknowledgements
This Standard specifies the requirements for a QMS incorporating
0 Introduction GMP, which is applicable to suppliers of both primary and
secondary packaging materials, origination/artwork and OINDP/
1 Scope complex materials to the pharmaceutical industry.
2 Normative reference The specific GMP requirements are dependent on the material
supplied and this Standard is structured according to these
3 Terms and definitions requirements.
Quality management Throughout this Standard the following terminology is used:
4
system • suppliers of products or materials to the pharmaceutical
5 Management responsibility industry are referred to as ‘the organization’
• the term ‘if appropriate’ is used several times, and where used,
6 Resource management is deemed to be ‘appropriate’ unless the organization can
document a justification otherwise
Measurement, analysis 1.2 Application

8
and improvement
This Standard applies during the life cycle of a material, whether
Guidance on risk design, manufacture or supply of packaging materials, origination/
A
management
artwork for medicinal products or OINDP/complex materials.
B This Standard is applicable for certification purposes to
PS 9000:2011. Whilst this Standard reflects requirements of
C Barcodes
ISO 9001:2008 and ISO 15378:2006 and may be utilized for
certification purposes, organizations cannot claim conformity
D Cleanrooms
unless their quality management systems conform to all the
E Drug Master Files (DMF) requirements of ISO 9001:2008 and/or ISO 15378:2006, although
certification assessments can be carried out simultaneously.
F
Scheme
G Bibliography
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2. Normative
reference
Home
Contents
Foreword
The following referenced documents are indispensable for the
Acknowledgements application of this Standard. For dated references, only the edition
0 Introduction cited applies. For undated references, the latest edition of the
referenced document (including any amendments) applies.
1 Scope ISO 9000:2005 Quality management systems – Fundamentals and
vocabulary
Quality management
4
system
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
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3. Terms and NOTE 2 In the case of continuous production, the batch is a

fraction of the production defined either as a fixed quantity or as
definitions
Home
How to use this document the amount produced in a fixed time interval.
[ISO 15378:2006, 3.5]
Contents
Foreword
The term ‘shall’ is used throughout this document to indicate those 3.4
Acknowledgements provisions which, reflecting the requirements of PS 9000:2011 are batch documentation
mandatory. documents and records that provide a history of the batch,
0 Introduction
including information relating to its production and control, and
Where the term ‘should’ is used within PS 9000:2011, it is which facilitate its traceability
1 Scope intended to indicate those provisions which are guidance. [ISO 15378:2006, 3.6]
2 Normative reference The following terms and definitions used are specific to Good
Manufacturing Practice (GMP) applicable to the manufacture 3.5
3 Terms and definitions of packaging materials for use in the packaging and labelling of batch number
medicinal products. lot number
Quality management unique identifier to identify a batch or lot
4
system
3.1 NOTE The batch number can be a combination of numbers,
5 Management responsibility admixture letters and/or symbols which identifies a batch and from which the
mix-up, stranger or rogue production and distribution history can be determined.
6 Resource management presence within the batch of one or more items, not of the nature of [ISO 15378:2006, 3.7]
that specified by the product description, i.e. cross-contamination
3.6
3.2 bracketing
8 assembly
and improvement matrix approach
Guidance on risk fitting together of packaging materials and/or components where the equivalence of the product or process has been proven,
A
management NOTE Examples may include pipette assemblies for filling, a reduction in the number of validation (PQ) batches, or a reduction
Guidance on verification prepared components of injection systems or positioning of needle of the number of technically identical machines/lines being subject
B
and validation requirements shields on pre-fillable syringes. to validation may be possible, using a bracketing and/or matrix
C Barcodes [ISO 15378:2006, 3.3] approach
D Cleanrooms 3.3 3.7

batch bio-burden
E Drug Master Files (DMF) lot level of viable micro-organisms on or in a manufacturing area,
defined quantity of material manufactured in one process or a equipment, raw or ancillary material, packaging component, bulk
F
Scheme series of processes, with the intent to have uniform characteristics product, intermediate, or finished packaging material
with consistent, homogeneous quality
G Bibliography
NOTE 1 To meet production requirements or customer needs, a
batch can be divided up into a number of sub-batches that are later
combined to form a single, consistent batch.
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3.8 3.13
Braille communicable disease
tactile reading and writing system composed of Braille cells, which disease of humans or animals caused by a micro-organism that
Home are a series of up to six raised dots set out in a domino-type cell can be spread from person (or animals) to person by transfer of
How to use this document used by the blind and partially sighted to enable identification of the that organism via physical contact, airborne particles or droplets
Contents medicinal product
[EN 15823:2010, 2.1]
3.14
Foreword complex material
Acknowledgements
3.9 material with a high degree of concern regarding route of
calibration administration with the likelihood of packaging component dosage
0 Introduction
process of checking or adjusting (by comparison with a reference form interactions, e.g. inhalation, injection
1 Scope standard) the accuracy of a measuring instrument
3.15
NOTE Calibration can also be described as the set of operations component
which establish, under specified conditions, the relationship constituent parts of an assembly
between values indicated by a measuring instrument or values
represented by a material measure, and the corresponding known 3.16
4
Quality management values of a reference standard. concurrent validation
system [ISO 15378:2006, 3.9] qualification and/or validation activities conducted in parallel with
5 Management responsibility the manufacture of commercial product where the product is
3.10 released before the conclusion of validation activities
6 Resource management change control
NOTE 1 Concurrent validation should follow the principles and
documented control of changes
procedures associated with prospective validation.
7 Product realization NOTE Changes may include, e.g. changes in raw materials,
NOTE 2 Concurrent validation applies to performance qualification
Measurement, analysis specifications, facilities, equipment, production processes and test
8 of the process only.
and improvement methods.
Guidance on risk [ISO 15378:2006, 3.10]
A
management
3.17
contamination
B
Guidance on verification 3.11
and validation requirements any kind of unwanted materials that may be incorporated into the
change parts
product
C Barcodes machine parts which are temporarily fitted to equipment to handle/
manufacture specific products, e.g. moulds, dies and transfer parts NOTE 1 Contamination may be physical, e.g. extraneous dirt
D Cleanrooms or dust; chemical, e.g. processing aids, lubricants or biological,
3.12 e.g. mould, fungus. This may be introduced, for example, from
E Drug Master Files (DMF) cleanroom equipment or air systems.
room in which the concentration of airborne particles is controlled, NOTE 2 A finished product can be contaminated by physical
Supplier Certification and which is constructed and used in a manner to minimize the
F (particulate), chemical or biological (bio- and endotoxin burden)
Scheme
introduction, generation, and retention of particles inside the room, action.
G Bibliography and in which other relevant parameters, e.g. temperature, humidity
and pressure are controlled, as necessary NOTE 3 Contamination can occur during production, packaging,
[ISO 15378:2006, 3.11] storage and/or distribution from contaminated air systems,
personnel, sampling equipment, materials, premises or containers.
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3.18 3.23
contract customer complaint
agreement customer information about deficiencies and/or nonconformities
Home legally binding document agreed between organizations on the NOTE 1 The information may be verbally communicated or
How to use this document provision of products or services written.
Contents NOTE Specifications and technical agreements may form part of a NOTE 2 The subject of a complaint can include packaging
Foreword contract. material quality, quantity or supply.
Acknowledgements [ISO 15378:2006, 3.16]
3.19
0 Introduction controlled area 3.24
controlled environment date of manufacture
1 Scope
area or environment constructed and operated to control the date when the first stages in the process of manufacture of the
possible introduction of potential contaminants product, irradiation date or the final release occurs
NOTE 1 The area is typically constructed and operated to control NOTE 1 The date of manufacture may be subject to customer
3 Terms and definitions the introduction of potential contamination and the consequences agreement in order that the appropriate shelf-life is commensurate
of accidental release of living organisms. with the risk of the products, and their intended use can be
Quality management
4
system NOTE 2 An appropriate pressure differential allows for the evaluated.
efficient removal of airborne contaminants, potential contamination NOTE 2 The date of manufacture may also be defined as the date
and the consequences of accidental release. of sterilization or of product release.
6 Resource management [ISO 15378:2006, 3.14]
3.25
7 Product realization 3.20 Design Qualification (DQ)
counterfeit process that verifies the suitability of the design
Measurement, analysis copy produced without authority with the intention of deceiving a
8
and improvement
user as to its true origin NOTE This may include the following to determine that the
Guidance on risk equipment is ready to be dispatched from the supplier to the
A
management organization and any development/optimization trials prior to the
3.21
B
Guidance on verification cross-contamination site acceptance test (SAT) (see 3.77):
contamination of a product with another product or material • appropriate risk analysis
C Barcodes NOTE Cross-contamination may also be referred to as admixture • user requirement specification (URS) (see 3.84)
(see 3.10), rogue, mix up and strangers. • contract specifications (may be a single document)
D Cleanrooms • factory acceptance tests (FAT) (see 3.30)
3.22
E Drug Master Files (DMF) 3.26
customer
Supplier Certification pharmaceutical manufacturer and/or the company which deviation
F
Scheme purchases the packaging materials departure from an approved standard operating procedure (SOP)
or established standard
G Bibliography
[ISO 15378:2006, 3.18]
NOTE These may also be referred to as incidents or
nonconformities.
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3.27 3.32
documented procedure Good Manufacturing Practice (GMP)
procedure that is established, documented, authorized, that part of quality assurance which ensures that products are
Home implemented and maintained, e.g. work instructions, standard consistently produced and controlled to the quality standard
How to use this document operating procedure, standing instruction appropriate to their intended use in the pharmaceutical industry
Contents and as required by the product specification
Foreword
3.28 [PS 9000:2001, 3.17]
double-check
Acknowledgements NOTE GMP and current Good Manufacturing Practice (cGMP)
secondary check
are equivalent. GMP guidelines are continually updated to the ever-
0 Introduction documented verification of an activity, result or record by a second
changing requirements of the state-of-the-art. This resulted in the
person or system
term cGMP sometimes being used.
1 Scope
NOTE A second in-process control check signature, production [ISO 15378:2006, 3.24]
and quality records for a batch signed by a second person or
electronic checks can be part of this verification process. Double- 3.33
checks typically are signed by a second person. in-process control
[ISO 15378:2006, 3.20] actions taken during the process to ensure product conformity to
4
Quality management its specification
system 3.29 NOTE 1 Monitoring processes and adjusting the means of
5 Management responsibility extractables
production can be necessary to meet product requirements.
compounds that can be extracted from elastomeric, plastic
6 Resource management compounds or coatings of the container and closure systems when NOTE 2 The control of the environment or equipment can also be
in the presence of appropriate solvents under vigorous conditions regarded as a part of in-process control.
7 Product realization [ISO 15378:2006, 3.26]
3.30
8
Factory Acceptance Test (FAT) 3.34
and improvement
contract specification Installation Qualification (IQ)
Guidance on risk documented verification process that the facilities, systems
A
management legal documented agreement between the organization and
customer and equipment, as installed or modified comply with the design
B
specification according to written approved specification/drawings
NOTE 1 FAT/contract specifications are signed by parties,
and manufacturer’s recommendations
C Barcodes agreeing terms and conditions for what is to be supplied.
NOTE 2 If FAT are required, the document should specify the 3.35
D Cleanrooms tests required and where these tests should be performed, and by intermediate product
whom. packaging material which has completed some but not all
E Drug Master Files (DMF) production stages
Supplier Certification 3.31 [ISO 15378:2006, 3.27]
F final inspection
Scheme
tests carried out on the finished product to determine compliance
G Bibliography with the specification
[ISO 15378:2006, 3.22]
Back Forward
3.36 NOTE 1 OINDP typically consist of a pharmaceutical formulation

line-clearance in a container closure that may act as, or be used in conjunction
removal (line purge) of everything associated with the prior with, a delivery device.
Home production run, and not required for the next production run NOTE 2 OINDP/complex materials may be primary or secondary
How to use this document materials and may require more stringent requirements for an
NOTE Line-clearance typically is done at the end of, or at the
Contents beginning of a production run, to prevent errors and OINDP.
Foreword cross-contamination (see 3.21)
Acknowledgements 3.41
3.37 Operational Qualification (OQ)
0 Introduction make-ready process to ensure the operation is doing what it is expected to
preparatory work and materials used in the setting up of a printing throughout the required operating parameters
1 Scope
or ancillary process prior to commencing the production batch NOTE OQ is typically a documented process that verifies that
2 Normative reference facilities, systems, equipment, as installed or modified, perform as
3.38 intended.
manufacturing
all operations of purchase of materials and packaging materials, 3.42
4
Quality management production, quality control, release, storage, distribution of products organization
system and the related controls suppliers of products or material to the pharmaceutical industry
5 Management responsibility [ISO 15378:2006, 3.29]
3.43
6 Resource management 3.39 origination
medicinal product artwork
7 Product realization any substance or combination of substances presented for treating all preparative artwork activities prior to print
or preventing disease in human beings or animals
Measurement, analysis NOTE 1 These include concept, design, graphics, reprographics,
8 NOTE 1 Any substance or combination of substances that may
and improvement film, plate making, silk screens and digital files and masters.
Guidance on risk be administrated to human beings or animals with a view to
A
management making a medical diagnosis or to restoring, correcting or modifying NOTE 2 Where packaging material is referenced within this
physiological functions in human beings or in animals is likewise Standard, this may include origination.
B [ISO 15378:2006, 3.32]
and validation requirements considered a medicinal product.
C Barcodes NOTE 2 Medicinal product may also be referred to as the 3.44
pharmaceutical or drug product including clinical trial products. Out Of Specification (OOS)
D Cleanrooms [ISO 15378:2006, 3.30] test results that do not comply with the specification
[ISO 15378:2006, 3.33]
E Drug Master Files (DMF) 3.40
Supplier Certification Orally Inhaled and Nasal Drug Products (OINDP) 3.45
F pharmaceutical dosage forms, typically liquids or solids, that are
Scheme overrun
delivered via the nose or mouth with the intention of topical delivery any material, outside of agreed tolerances, produced in excess of a
G Bibliography to the nasal passage, airways or lungs, as opposed to the customer specific order quantity
gastro-intestinal tract
Back Forward
3.46 NOTE These may include anti set-off spray powders, mould
packaging materials/components release agents, compressed air, rolling lubricants, which facilitate
materials used in pharmaceutical packaging which include primary the manufacturing or handling process and may be removed at the
Home and secondary packaging materials final processing stage.
Contents 3.47 3.51
Performance Qualification (PQ) product
Foreword
documented verification that the facility, systems and equipment finished packaging material/component or combination of
Acknowledgements components completed to an agreed specification, which is
as connected together, can perform effectively and reproducibly
0 Introduction based on approved process method and specifications supplied to the pharmaceutical manufacturer/customer
NOTE PQ consists of a series of documented challenge tests
1 Scope 3.52
of the overall line performance to ensure that it can consistently
product release
produce the desired output at the required standard.
2 Normative reference decision to release the product for sale or supply, following a
formal review performed by the quality unit or a person authorized
3.48
3 Terms and definitions by the quality unit(s)
primary packaging materials/component
[ISO 15378:2006, 3.8]
4
Quality management materials used in pharmaceutical packaging which will contain,
system seal or be used for dose application and will have direct contact
3.53
5 Management responsibility with the medicinal product
product security
NOTE 1 Primary packaging materials are, e.g. glass, rubber, those procedures and practices designed, specifically, to ensure
6 Resource management plastics, aluminium containers/components, films, foils, laminate that pharmaceutical packaging products are free from
containers/components. They may be combinations of different cross-contamination, are correctly identified and prevent
7 Product realization materials/components, e.g. syringes, aerosol valves. unauthorized use
Measurement, analysis NOTE 2 Primary packaging materials with limited contact, e.g. NOTE Product security controls also extended to the control of
8
and improvement
pipettes, syringes are included within the scope of this Standard. print media, reject and waste material including overruns.
Guidance on risk
A NOTE 3 Primary packaging materials may be printed or
management
decorated. 3.54
B
Qualification Process (QP)
3.49 process to demonstrate the ability to fulfil specified requirements
C Barcodes print impression media NOTE Qualification, comprises DQ (see 3.25), IQ (see 3.34),
generic term for any type of physical media that creates the image OQ (see 3.41), SAT (see 3.77), and PQ (see 3.47), as well as
D Cleanrooms
in ink, e.g. plates, cylinders, screens re-qualification and revalidation as appropriate. This activity can
[PS 9000:2001, 3.27] also be performed concurrently, by bracketing (matrix validation)
(see 3.6), and/or retrospectively.
F
Supplier Certification 3.50
Scheme processing aids 3.55
G Bibliography ancillary materials Quality Management System (QMS)
materials not included in the product specification set of interrelated or interacting elements that organizations use to
direct and control how quality policies are implemented and quality
objectives are achieved
Back Forward
3.56 3.61
quality records reconciliation
general and product-specific records of an organization which, comparison between the amount of product and identification
Home when considered as a whole, enable a realistic assessment of labels theoretically and actually produced or used, making
How to use this document quality. They provide traceability and allow reconstruction of earlier allowance for normal variation
Contents events NOTE The comparison considers waste, samples or other losses
Foreword NOTE Examples of such records include maintenance, training, inherent in the process.
Acknowledgements calibration, validation, auditing, change control, design, buying, [ISO 15378:2006, 3.44]
production and test results, retained samples, area and equipment
0 Introduction
cleaning and line-clearance. 3.62
[PS 9000:2001, 3.29] rejected
1 Scope
status of starting materials, process aids, intermediate products
3.57 or finished products whose test results do not comply with one or
quality critical more of the requirements of the specification, and which have been
parameter affecting packaging material and/or medicinal product deemed, usually by the quality unit (see 3.58), as not suitable for use
quality [ISO 15378:2006, 3.46]
Quality management
4 NOTE A material, process step or process condition, test
system
requirement or any other relevant parameter can be considered to
3.63
5 Management responsibility reprocessing
be quality critical if nonconformity to its requirements could have
repeating part of a production process to meet specified
significant detrimental consequences.
6 Resource management requirements
[ISO 15378:2006, 3.40]
NOTE Continuation of part of a process after an in-process
7 Product realization 3.58 control test has shown that the part is incomplete, is considered to
Measurement, analysis quality unit be part of the normal process, and is not reprocessing.
8
and improvement independent unit responsible for ensuring that the various [ISO 15378:2006, 3.48]
Guidance on risk operations associated with the quality management system are
A
management appropriately planned, approved, conducted and monitored 3.64
Guidance on verification retained samples
B
and validation requirements 3.59 materials or finished products stored for future reference
C Barcodes quarantine NOTE These samples are generally taken in a sufficient amount
status of materials or products isolated (physically or by other and stored under recommended conditions for reference during a
D Cleanrooms effective means), pending a decision on their subsequent defined period of time.
disposition [ISO 15378:2006, 3.49]
3.60
Supplier Certification realization
F
Scheme
generic term which covers all processes required to achieve the
G Bibliography desired output from design to product delivery
[ISO 15378:2006, 3.43]
Back Forward
3.65 3.67
retrospective validation risk
validation of a process, based on accumulated historical effect of uncertainty on objectives
Home production, testing, control, and other information for product/ NOTE 1 An effect is a deviation from the expected – positive and/
How to use this document equipment already in production and distribution or negative.
Contents NOTE 1 This approach includes establishing documented NOTE 2 Objectives can have different aspects.
Foreword evidence that installed and operating equipment produces
a consistent product by performing a historic review of data NOTE 3 Risk is often characterized by reference to potential
Acknowledgements
generated over a range of operating parameters and raw materials. events and consequences or a combination of these.
0 Introduction
NOTE 4 Risk is often expressed in terms of a combination of the
NOTE 2 Validation should be performed against a number
of batches, against written specifications or predetermined consequences of an event (including changes in circumstances)
1 Scope
expectations. and the associated likelihood of occurrence.
[ISO 31000:2009, 2.1]
2 Normative reference NOTE 3 The number of batches to review will depend on
the process/equipment but, in general, data from ten to thirty 3.68
consecutive batches should be examined to assess process risk analysis
Quality management consistency. The review should include any batches that failed to systematic use of available information to identify hazards and to
4
system meet specifications. This review may include maintenance and estimate the risk
engineering records, quality records, and customer complaints. [ISO 15378:2006, 3.52]
NOTE 4 On completion of a retrospective validation activity, NOTE Risk analysis provides the basis for risk evaluation.
6 Resource management conclusions relating to all key operating parameters should be
documented in the form of a validation report. 3.69
7 Product realization risk assessment
3.66 overall process of risk identification, analysis and evaluation
Measurement, analysis [ISO 31000:2009, 2.16]
8 rework
and improvement
Guidance on risk action on a nonconforming product to make it conform to the 3.70
A requirements
management risk control
Guidance on verification NOTE Sorting can be considered to be rework. describes the actions of implementing risk management decisions
B
[ISO 15378:2006, 3.51]
C Barcodes
3.71
risk evaluation
D Cleanrooms process of comparing the results of risk analysis to determine
whether the risk and/or its magnitude is acceptable or tolerable
E Drug Master Files (DMF) [ISO 3100:2009, 2.26]
F
Supplier Certification 3.72
Scheme risk management
G Bibliography collective activities undertaken by the organization to identify,
assess, and prioritize risks followed by coordinated and
economical application of resources to minimize, monitor, and
control the probability and/or impact
Back Forward
3.73 3.78
risk management framework specification
set of components that provide the foundations and organizational document stating requirements
Home arrangements for designing, implementing, monitoring, reviewing [ISO 15378:2006, 3.57]
How to use this document and continually improving risk management throughout the NOTE A specification can be related to activities, e.g. procedure
Contents organization document, process specification and test specification, or
Foreword NOTE 1 The foundations include the policy, objectives, mandate products, e.g. product specification, performance specification and
Acknowledgements and commitment to manage risk. drawing.
0 NOTE 2 The risk management framework is embedded within the
Introduction
organization’s overall strategic and operational policies and practices.
3.79
starting material
1 Scope [ISO 31000:2009, 2.3]
raw material/components/substances used in order to produce
3.74 packaging materials
risk reduction [ISO 15378:2006, 3.59]
3 Terms and definitions systematic approach taken to reduce the probability or
consequence of risks 3.80
4
Quality management sterile
system state of being free from viable microorganisms
3.75
5 Management responsibility secondary packaging materials/component [ISO 15378:2006, 3.60]
non-contact packaging materials; generally includes printed or
6 Resource management unprinted cartons, labels, leaflets or inserts (or outserts), 3.81
over-wraps and transit containers such as shipping boxes subcontractor
7 Product realization third party for outsourced work and services which contribute in
3.76 full, or part, to the manufacture of packaging materials
Measurement, analysis shelf-life
8 [ISO 15378:2006, 3.61]
and improvement
period during which a packaging material is expected to comply
A
Guidance on risk
with the requirements (specifications) when stored under defined 3.82
management supplier
conditions and after which it should not be used
Guidance on verification the organization that provides materials/services to the packaging
B
3.77 material manufacturer
C Barcodes Site Acceptance Test (SAT)
Site Acceptance Tests may verify that IQ/OQ (see 3.34, 3.41) has 3.83
D Cleanrooms been completed successfully by means of a simulated production traceability
run using actual production materials ability to trace the history, application or location of that which is
E Drug Master Files (DMF) under consideration
NOTE The output should be monitored and measured and the
Supplier Certification results used to determine if performance qualification is required. NOTE When considering product, traceability can relate to:
F
Scheme
SAT may be equivalent to one performance qualification run. • the origin of materials and parts
G Bibliography • the processing history
• the distribution and location of the product after delivery
[ISO 15378:2006, 3.63]
Back Forward
3.84 3.88
User Requirement Specification (URS) verification
approved document that states each functional, operational and/or confirmation through the provision of objective evidence that
Home technical attribute of the equipment or process required to produce specified requirements have been fulfilled
How to use this document the desired material NOTE 1 The term ‘verified’ is used to designate the corresponding
Contents NOTE The planning stage should include the development of a status.
Foreword URS. This may include consideration for equipment layout with NOTE 2 In development and design, verification is the process
Acknowledgements sufficient space for material flow and operators, availability of spare of examining the results of an activity under consideration in
parts, ease of access for cleaning and line clearance. Alternatively, order to establish whether said activity conforms to the specified
0 Introduction
this information may be provided in other documentation. requirements.
1 Scope [ISO 15378:2006, 3.65]
3.85
validation 3.89
confirmation, through the provision of objective evidence that the working areas
requirements for a specific intended use or application have been defined area where origination, production, test or inspection
consistently fulfilled operations are carried out and which will be subject to a
4
Quality management [ISO 15378:2006, 3.64] line-clearance
system
NOTE 1 Qualification (see 3.54) and validation comprise DQ NOTE These areas are physically defined by the use of barriers,
5 Management responsibility (see 3.25), IQ (see 3.34), OQ (see 3.41), SAT (see 3.77), and floor marking or similar means of definition, and may contain
PQ (see 3.47), as well as re-qualification and revalidation as equipment, e.g. production machinery, test equipment, computers,
6 Resource management appropriate. work benches, proofing equipment.
7 Product realization NOTE 2 Validation can also be performed concurrently, by
bracketing/matrix approach and/or retrospectively (see 3.6).
8
and improvement 3.86
Guidance on risk Validation Master Plan (VMP)
A
management document describing how the validation of the equipment and/or
B
Guidance on verification processes will be accomplished, listing the key responsibilities and
and validation requirements order of execution of the activities
C Barcodes
3.87
D Cleanrooms Validation Summary Report (VSR)
summary following completion of all stages of qualification (DQ, IQ,
E Drug Master Files (DMF) OQ, PQ) which concludes the validation process
F
Scheme
G Bibliography
Back Forward
• the intentions and approach to validation and change control

4. Quality management which shall be documented
Guidance
system
Home
The organization should have a documented business continuity plan
(see BS 25999 Business continuity management).
Contents
Foreword 4.2.2 Quality manual
4.1 General requirements
Acknowledgements A documented quality manual shall be established which details
a) A quality management system shall be developed and the scope of the quality management system and defines the
0 Introduction documented which includes the organizational structure, extent to which this Standard is applicable to its processes and
procedures, processes and resources within the organization. outputs, which includes:
1 Scope
b) The organization shall specify the processes required and detail • exclusions from this Standard, which shall be documented and
2 Normative reference how they interface with each other. These processes shall be justified
analysed to facilitate the implementation of systematic continual
improvement. • reference to procedures which have been established and
documented and outlines the structure of the documentation
c) The organization shall ensure that the necessary resources are
4
Quality management used in the QMS
system available to support these processes and their operation of is
effective. • a description of the interface between the processes within the
5 Management responsibility QMS
d) The organization shall describe its overall policy, intentions and
6 Resource management approach to the assurance of product quality, in the QMS. 4.2.3 Control of documents
e) The organization shall define the controls required to ensure that
a) The QMS shall include a documented procedure for the control
outsourced product and processes are suitably managed based
of documents, which incorporates periodic reviews.
Measurement, analysis on their criticality, in the QMS.
8
and improvement This includes defining how the controls are managed between b) QMS documents shall be approved prior to issue, and changes
the organizations. reviewed by the original approving function or an appropriate
Guidance on risk
A designated function with sufficient knowledge.
management f) The organization shall include an independent quality unit that is
B
Guidance on verification both impartial and separate from production c) Controlled documents shall include a unique identification,
and validation requirements version control and effective date to ensure only the correct
(see 5.5.3 & 5.5.4).
C Barcodes versions are available where required.
4.2 Documentation requirements d) Where the organization requires the use of external
D Cleanrooms documentation, it shall be identified and distributed in a
4.2.1 General
controlled manner.
E Drug Master Files (DMF) The organization shall define the documentation within its system,
which includes: e) There shall be a documented procedure for managing obsolete
Supplier Certification documents. This shall include controls to prevent unintentional
F • the organization’s overall quality policy, objectives and quality
Scheme
use and include a defined period for the retention of at least one
manual, including procedures and records required by this obsolete copy.
G Bibliography
Standard (see 4.2.4)
• documents required to facilitate effective planning, operation
and control of the organization’s processes
Back Forward
f) Changes to documentation shall be communicated to all Guidance

personnel impacted, through appropriate training. Electronic, photographic or other data processing systems, used instead of
Evidence of this training shall be recorded (see 4.2.4). written documents should be validated to ensure that the integrity of the data
Home
g) Electronic signatures on documents shall be controlled to the is maintained during the period of anticipated storage. Data stored by these
How to use this document equivalent security level given by a hand-written signature. systems should be accessible in legible form. Electronically stored data should
Contents be protected against loss or damage of data, e.g. by duplication or back-up and
Foreword
4.2.3.1 System administration transferral onto another storage system.
Acknowledgements a) The organization shall assign responsibility for ensuring
For further details on information (and data) security management
that information technology and the data itself is secure and
0 Introduction
see ISO/IEC 27001, ISO/IEC 27002 and GAMP.
maintained according to documented procedures.
1 Scope
b) The organization shall ensure only authorized personnel have 4.2.4 Control of records
access to systems and files for the purpose of installation,
a) A documented procedure shall be established for the
2 Normative reference maintenance, repair, recovery or system upgrades.
management and control of records within the quality
c) There shall be a documented policy covering password management system.
3 Terms and definitions management and security routines including ‘sleep mode’,
b) This procedure shall define the identification, storage, protection,
which shall exist to cover periods of personnel absence from the
4
Quality management and disposition of records. Records shall be readily retrievable.
system computer.
c) Records in electronic format shall be managed and controlled to
5 Management responsibility d) Access to work files and data shall be limited by network or file
the same level as those required for other records.
security to ensure only authorized users are able to manipulate
6 Resource management data files. d) Entries in records shall be clear, indelible, and legible and made
directly after performing the activity, in the order performed.
e) Artwork files shall be named and stored according to a
7 Product realization Corrections for entries shall be dated, initialled or signed, and,
documented procedure that enables them to be readily
where appropriate, explained, leaving the original entry still
Measurement, analysis identified, issue controlled and traceable. When files are stored
8 legible.
and improvement in a shared area such as a file server, accessed by several
Guidance on risk workstations, there shall be a documented procedure to ensure e) Quality critical processes, stages and parameters requiring a
A double/secondary check shall be defined by the organization,
management file integrity.
Guidance on verification including those necessary in production and for the product
B f) The organization shall have a documented procedure for the
and validation requirements release.
back-up and recovery of electronic product related data, which
C Barcodes defines the frequency of back-up, the method and media to be f) Where double/secondary checks are defined, records shall
used, and the physical process for safe storage of the data files. clearly demonstrate the identified check and stage. If either
D Cleanrooms Back-up media shall be clearly identified and traceable. check is carried out electronically, this shall be clearly defined
within the process.
E Drug Master Files (DMF) g) The organization shall have a documented Information
Technology (IT) recovery plan which details the system for g) The organization shall maintain records to ensure identification
Supplier Certification partial and total recovery of data in the event of a failure of the IT and traceability for each batch of packaging material.
F
Scheme
system. The system shall be validated and challenged at defined h) Records shall demonstrate the quantity manufactured, and
G Bibliography intervals to ensure the information can be restored. quantity approved for distribution.
h) Access to legacy systems shall be defined as part of change i) The organization shall identify stages in their process where the
control, if IT systems are changed. product documentation is verified and approved.
Back Forward
j) All relevant records shall be retained for at least five years after
the date of manufacture of the packaging material, or as agreed
with the customer.
Home
k) In the event of mergers, acquisition, facility closure or impending
How to use this document business cessation the organization shall advise the customer
Contents so that appropriate contingency arrangement can agreed for the
Foreword retention of records.
Acknowledgements
Guidance
0 Introduction Records comprise batch-related manufacturing data as well as other quality
records, e.g. deviation and investigation reports, training records, validation
1 Scope reports.
Quality management
4
system
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
Back Forward
5.3 Quality policy

5. Management a) The quality policy shall be defined, signed and implemented by
the organization’s senior management, ensuring the policy is
responsibility
Home
appropriate to the business.
Contents
b) The quality policy shall state the business commitment to the
requirements of its intended standard(s) and be communicated
Foreword
5.1 Management commitment throughout the organization.
Acknowledgements
Senior management shall demonstrate its level of commitment c) The quality policy shall include a review process for the business
0 Introduction in the execution, development and continual improvement of the and quality objectives.
organization’s approach to quality management systems through: d) The quality policy shall outline the business framework
1 Scope
• a defined quality policy for reviewing the effectiveness and suitability of its quality
2 Normative reference • communicating the importance in the achievement of customer management system together with its commitment to continual
satisfaction and compliance with appropriate regulations and improvement.
3 Terms and definitions standards e) The quality policy shall include statements on:
• establishment of quality objectives
Quality management • how security of the product will be assured
4
system
• the provision of resource
• how a hygienic, clean and controlled environment will be
• execution of a management review process
5 Management responsibility established and maintained
• ensuring roles, responsibilities and authorities are defined,
• the extent to which this Standard will be used in the
communicated and implemented throughout the organization
6 Resource management organization
5.2 Customer focus
7 Product realization 5.4 Planning
Senior management shall ensure customer focus is managed
Measurement, analysis throughout the organization; ensuring customer requirements are 5.4.1 Quality objectives
8
and improvement met and communicated, with the aspiration of enhancing customer a) Senior management shall ensure quality objectives are
Guidance on risk satisfaction (see 8.2.1). established within the organization, which are consistent with the
A
management
quality policy.
B
Guidance on verification 5.2.1 Customer audits
and validation requirements b) The quality objectives shall be specific, measurable and include
The organization shall approve access, by mutual agreement, for any requirements needed to meet the product requirements
C Barcodes existing/prospective customers or their nominated representative(s) (see 7.1).
to conduct audits in order to review and assess the organization’s
D Cleanrooms
quality management system. 5.4.2 Quality management system planning
E Drug Master Files (DMF) Guidance a) Planning of the quality management system shall ensure the
Key examples of customer requirements for organizations include: requirements given in 4.1 and the quality objectives are met.
F
Scheme • suitable facilities b) Senior management shall ensure the quality management system
• competent and trained personnel integrity is maintained when changes are planned and implemented.
G Bibliography
• processes designed to ensure product security
• avoidance of cross-contamination and the ability to consistently produce
product conforming to the customer specifications
Back Forward
5.5 Responsibility, authority and communication • approve or reject products manufactured, processed, packed,
or held under contract by another organization
5.5.1 Responsibility and authority • review and approve reprocessing
Home a) Senior management shall ensure effective communication of the • approve all defined changes
How to use this document defined responsibilities and authorities within the organization.
Contents b) The organization shall maintain a record of signatures of
5.5.4 Quality unit responsibility
Foreword responsible persons (see 4.2.4). The quality unit(s) shall have the responsibility for quality critical
Acknowledgements decisions independently from production to:
c) Any person with responsibility for product quality decisions shall
have the authority to make those decisions independently. • approve or reject all written procedures or changes to those
0 Introduction
procedures, for production and process control(s) designed to
1 Scope 5.5.2 Management representative assure product quality and integrity
The management representative shall be appointed by the senior • approve or reject any deviations from the documented
2 Normative reference management and shall form part of the organization’s management procedures referenced in 5.5.3
team. • approve or reject specifications, standards, sampling plans,
3 Terms and definitions test procedures, or other laboratory control mechanisms as
Irrespective of other responsibilities, the designated representative well as changes to these documents
4
Quality management shall have overall responsibility and authority for the organization’s • review any complaint involving the possible failure of a product
system quality management system, which includes: to meet any of its specifications and, for such products,
5 Management responsibility • the identification and coordinated implementation of processes determining the need for an investigation
required for an effective QMS ensuring the processes • review and approve any investigation conducted in accordance
6 Resource management established are effectively maintained with 5.5.3
• reporting of quality management performance to senior • review and assess suppliers
management along with any opportunity for improvement • approve validation, verification and qualification documents
Measurement, analysis • promotion and awareness of customer requirements and
8 5.5.5 Internal communication
and improvement expectations throughout the organization
Guidance on risk a) Senior management shall establish appropriate processes for
A Guidance
management
effective communication across the organization, which includes
Guidance on verification This representative can also liaise with external parties on matters that relate to
B information relating to the performance and effectiveness of the
and validation requirements the quality management system.
quality management system.
C Barcodes
5.5.3 Quality unit authority b) The organization shall ensure appropriate systems are
established to communicate GMP and regulatory requirements,
D Cleanrooms The quality unit(s) with responsibility for quality critical decisions
quality policies, quality objectives and procedures throughout
shall have the authority independently from production to:
each level of the organization.
E Drug Master Files (DMF) • approve or reject all raw materials, components, in-process
c) Senior management shall be notified in a timely manner of
Supplier Certification materials, product and labelling
F quality critical situations, in accordance with a documented
Scheme • review production records to ensure no errors have occurred
procedure.
and, if errors have occurred, that they have been fully
G Bibliography
investigated and satisfactorily resolved
Back Forward
Guidance Guidance
Examples of senior management quality critical communication should be The process of management review should demonstrate a proactive approach
clearly defined, e.g. product recalls, admixture, quality critical defects. based on historical data and information.
Home
Examples of communication processes include those related to the The organization’s approach to management review will vary and should be
How to use this document communication of the quality policy, management review, internal quality audit determined by the organization, e.g. may be a monthly process with an annual
Contents results, and corrective and preventive actions. summary review not just a six monthly/annual cycle.
Foreword The process should ensure that all areas of input, output and review are fully
Acknowledgements 5.6 Management review addressed throughout the review cycle.
0 Introduction 5.6.1 General

a) There shall be a review of the organization’s quality
1 Scope management system by senior management. This shall take
place at defined and planned intervals, to ensure the continued
2 Normative reference suitability, adequacy and effectiveness of the QMS.
3 Terms and definitions b) The review shall include an assessment of opportunities for
improvement, (see 8.5) and the need to make any changes.
Quality management This shall include the quality policy and quality objectives. The
4
system
records of these management reviews shall be maintained
5 Management responsibility (see 4.2.4).
6 Resource management 5.6.2 Review input

The input into the management review process shall incorporate,
7 Product realization as a minimum, information on:
Measurement, analysis • first, second and third party audit results
8
and improvement
• feedback from customers
Guidance on risk • process performance and conformity
A
management
• corrective and preventive action status and trends
Guidance on verification • review of actions from previous reviews
B
• review of changes that could affect the quality management
C Barcodes system
• improvement recommendations and change control
D Cleanrooms • effectiveness of training and future training needs
E Drug Master Files (DMF) 5.6.3 Review output

Supplier Certification The documented output from the management review shall detail
F
Scheme any decisions and actions related to the:
G Bibliography • effectiveness of the quality management system, and
processes
• improvement of products and/or customer requirements
• resources including training requirements
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f) Maintain records including personnel education, training, skills

6. Resource and experience (see 4.2.4).
g) Where consultants are employed to advise on quality matters,
management
Home
records of their qualifications and type of service(s) provided
How to use this document shall be maintained (see 4.2.4).
Contents
h) Provide additional refresher training at defined intervals.
Foreword
6.1 Provision of resources
Acknowledgements 6.2.2.1 Appropriate training shall cover all the organization,
Senior management shall implement and maintain the quality temporary and contract personnel and include awareness of:
0 Introduction management system through continual improvement and
effectiveness reviews in order to meet both the business and • GMP and the appropriate contents of this Standard
1 Scope customer requirements. They shall also determine and provide the • risk of product cross-contamination (see 7.5.1.1)
resources needed to meet the requirements of this Standard. • the implications resulting from any deviations from specified
2 Normative reference procedures, processes or specifications
6.2 Human resources • potential hazard to end product user/patient if product is
3 Terms and definitions cross-contaminated, e.g. admixture
Quality management
6.2.1 General • impact on customer’s product quality of any departures from
4 specified procedures
system Personnel performing work affecting product quality shall
demonstrate competence through a combination of appropriate
5 Management responsibility 6.2.2.2 The organization shall provide means of evaluating the
education, qualification, training, skills and/or prior experience
applicable to the role and activities to be undertaken. understanding and competence level achieved against the training
provided/delivered.
7 Product realization 6.2.2 Competence, awareness and training
6.2.2.3 The organization shall establish a documented policy/
Senior management are responsible for development and procedure detailing appropriate awareness training for personnel
8 implementation of an effective training culture, which addresses all
and improvement visiting the manufacturing location, e.g. temporary personnel and
Guidance on risk levels throughout the organization and shall: contractors.
A
management a) Ensure that personnel performing work, that impacts product
B
Guidance on verification quality, be demonstrably competent to carry out their activity 6.2.2.4 Additional and appropriate refresher training shall be
and validation requirements conducted at defined intervals and include awareness of applicable
through training, work experience and qualification, or a
C Barcodes combination thereof. GMP, procedures and policies that affect product quality and the
quality management system.
b) Ensure personnel, including temporary and contract employees
D Cleanrooms are appropriately trained prior to commencing work.
E Drug Master Files (DMF) c) Provide training through competent personnel and/or e-learning 6.2.2.5 Particular attention shall be given to training of the
methodology. personnel involved with the manufacture of sterile components
Supplier Certification or components to be subsequently sterilized.
F d) Continually review and evaluate the effectiveness of the training
Scheme
program and provide required updates.
G Bibliography 6.2.2.6 Where applicable, training on microbiological and
e) Ensure personnel understand the impact of their activities and particulate contamination prevention and the potential risks to
how they contribute to the overall quality objectives. the patient/end user shall be provided.
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Guidance • changing, toilet and hand-washing facilities shall be provided

Senior management should ensure a training matrix is developed, implemented for areas where products are processed and handled; these
and maintained. facilities shall be separate from manufacturing areas and not
Home ventilated directly to the manufacturing area
How to use this document 6.3 Infrastructure f) Storage areas shall be:
Contents • of adequate capacity to allow orderly storage of starting
Senior management shall manage, operate and maintain an
Foreword infrastructure of suitable size, location, construction and design materials and products
Acknowledgements to facilitate maintenance, prevent contamination and enable the • clean and dry with provision to store materials, products and
production of products of appropriate quality through the provision change parts, off the floor, and allow the dry storage of pallets
0 Introduction
of: g) Outdoor storage of starting materials shall only be permitted
1 Scope a) Suitable buildings, workspace, utilities and support services. under exceptional circumstances and justified by a documented
assessment of contamination risk.
b) Process equipment, hardware and software.
2 Normative reference h) Where product is exposed, light fittings shall have coated lighting
c) Adequate maintenance of facilities and equipment. tubes or protective safety covers.
3 Terms and definitions d) Procedures for the handling and ensuring the safe disposal of i) Drains, located in the processing or storage areas to aid removal
Quality management waste, reject and recycled materials to minimize the risk of of extraneous materials or spillages, shall be sized to suit the
4
system re-entry into the supply chain (see 7.5.1.7). operations carried out and have trapped gullies; open channels
5 Management responsibility e) An infrastructure that is managed, operated and maintained in are to be avoided but, where necessary, they shall be shallow to
accordance with GMP to avoid product contamination, including facilitate cleaning and disinfection.
6 Resource management but not limited to:
Guidance
• facilities shall be secure against entry of unauthorized Facilities and equipment should be located, designed, constructed, adapted and
personnel maintained to suit the operations to be carried out.
Measurement, analysis • personnel who do not work in production, storage or quality
8 Interior surfaces (walls, floors and ceilings) should be smooth, free from cracks
and improvement control/quality assurance shall only access these areas
and open joints to permit effective cleaning.
Guidance on risk through clearly-defined gangways, wearing appropriate
A Facilities should be laid out to permit operations to take place in a logical
management protective clothing
Guidance on verification • layout, design and operation shall minimize the risk of errors sequence.
B Lighting, temperature, humidity and ventilation should not adversely affect,
and validation requirements and permit effective cleaning and maintenance to avoid
cross-contamination, build up of dust, dirt or moulds and, in directly or indirectly, either the products during their manufacture and storage or
C Barcodes
general, any adverse effect on the quality of products the correct functioning of equipment.
• working areas shall be defined and segregated to avoid Production and storage areas should be effectively ventilated appropriate for
D Cleanrooms
cross-contamination the:
E Drug Master Files (DMF) • where physical barriers are used to segregate working areas • products handled
they shall be a minimum of 1.5 metres high and continuous • operations undertaken
Supplier Certification from floor level, unless an alternative is justified through a • influence of the external environment
F
Scheme
documented risk assessment Pipe-work, light fittings, ventilation points and other services should be designed
G Bibliography • inspection and sorting areas shall be defined and segregated and sited to avoid creating recesses which are difficult to clean.
by physical barriers of a minimum of 1.5 metres high and
continuous from floor level unless an alternative is justified
through a documented risk assessment
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6.4 Work environment c) Handling/transfer containers shall be clean and not contribute
a) The organization shall establish documented requirements for to particulate contamination. For product contact packaging
health, cleanliness, clothing and access control of personnel, materials they shall be covered or appropriately sealed.
Home
if contact between such personnel and the packaging material d) Pallets shall be constructed of materials appropriate to the product
or work environment could adversely affect the quality of the being handled. They shall be clean, dry and in good condition.
Contents packaging material. Pallets shall be stored in appropriate conditions that ensures they are
Foreword
b) The requirements for environmental conditions during not exposed to prolonged periods in the open air or the elements.
Acknowledgements production and packaging shall be assessed jointly between the e) The organization shall define and provide appropriate protective
0 Introduction organization and the customer or as defined by this Standard. clothing.
1 Scope c) For primary packaging materials, the appropriate f) Where primary packaging materials are exposed, e.g.
environmental conditions shall be defined and applied as machine out-feeds, covers shall be used unless justified
2 Normative reference detailed in this Standard or as specified by the customer through a documented risk assessment.
(see 7.2.3 and 7.2.3.2).
3 Terms and definitions g) For the production and processing of primary packaging
d) The conditions and results of environmental monitoring and
Quality management contamination control for production shall be documented materials, operator clothing shall include protective garments
4 and hair covering.
system and reviewed as part of the organization’s continual
5 Management responsibility improvement programme.
Guidance Guidance
For primary packaging materials an environmental cleanliness gradient The minimum environmental conditions are appropriate for the processing of
7 Product realization should exist from the input of raw materials to the production of the secondary packaging materials and are also suitable for product contact materials,
converted item and through to the inspection, collation and transit unless higher environmental conditions are specified by the customer.
Measurement, analysis packaging, i.e. a progressively cleaner processing environment as the The use of automatic door closers, protective air curtains or plastic curtains
8
and improvement
product moves through the stages of manufacture. should be implemented, where appropriate.
Guidance on risk Consideration should be given to the use of heat-treated pallets to minimise
A
management
contamination through migration of any chemicals used in other pallet
B
Guidance on verification 6.4.1 Environmental conditions treatments.
The organization shall operate appropriate environmental
C Barcodes conditions for processing the product.
6.4.2 Classification of clean areas/cleanrooms
D Cleanrooms 6.4.1.1 Minimum environmental conditions
Clean areas/cleanrooms shall be classified according to
a) Any ventilation or air extraction system shall contain a filter
E Drug Master Files (DMF) ISO 14644-1, and monitored/operated according to ISO
medium which prevents the introduction of visible contaminants
14644-2, ISO 14644-3 and ISO 14644-5 or equivalent.
F
Supplier Certification or insects into the processing or handling areas.
Scheme
b) Doors shall be kept closed except when in use. Windows in Guidance
G Bibliography or immediately adjacent to production and associated storage For cleanroom design, construction and start-up see ISO 14644-2.
areas shall be closed or effectively screened. Monitoring may be conducted in accordance with ISO 14698-1 and
ISO 14698-2.
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6.4.3 Risk control of contamination b) The organization’s overall pest protection requirements shall be
detailed in documented procedures and schedules.
6.4.3.1 Hygiene and security
c) Where any infestation is identified, immediate action shall be
Home a) The organization shall define a documented procedure detailing taken to eliminate the hazard and any preventive and control
How to use this document requirements for health, hygiene practices and protective measures shall not introduce contamination into the product.
Contents clothing for all personnel who are required to go into processing
and storage areas. d) Electrical fly-killing units and crawling-insect traps shall
Foreword be suitably sited and maintained so as not to inadvertently
Acknowledgements b) The organization shall determine, document and implement contaminate products. Windows in or immediately adjacent to
policy(s) requirements for the control of risks, which may result in production and associated storage areas shall be closed or
0 Introduction contamination of packaging materials, relating to: effectively screened.
1 Scope • wearing of jewellery, including watches, piercing(s)
• wearing of make-up Guidance
• smoking, eating, chewing, drinking, and personal medication Where doors are in constant use, it is recommended that they should be
• handling and disposal of waste operated with an automated system.
• personal hygiene and health An approved pest-control contractor should be employed, providing regular
inspection reports for organization review.
• protective clothing, including hair and footwear
4
Quality management The use and location of insecticides, rodenticides and disinfectants should be
system controlled, and records kept of their use.
• microbiological contamination
6.4.5 Materials and utilities
6 Resource management c) Hygiene requirements shall be prominently displayed at all 6.4.5.1 General
entrances to processing and storage areas.
7 Product realization a) Processing aids shall be defined and be subject to a
d) Contractors and visitors to sites of material/product processing, documented risk assessment for their potential impact on the
Measurement, analysis handling or storage shall be notified of and comply with the quality of the packaging materials.
8
and improvement hygiene and cross-contamination avoidance requirements.
Guidance on risk b) Reusable handling/transfer containers used to hold starting
A
management
e) Persons with skin lesions, dermatitis or known communicable materials during processing shall be subjected to a documented
diseases shall not come into direct contact with the starting cleanliness check before being loaded with a different material
B materials, processing equipment or the product.
and validation requirements to avoid cross-contamination.
f) Personnel shall be trained in and required to adopt hygienic
C Barcodes
practices, e.g. hand-washing. 6.4.5.2 General requirements for primary
D Cleanrooms g) All personal medicines shall be controlled and, except where
packaging materials
specifically approved and documented, not taken into the areas a) Starting and processing aids, which may come into
E Drug Master Files (DMF) where materials or products are processed, handled or stored. direct contact with the medicinal product, shall be of the
appropriate standard and controlled.
F
Scheme 6.4.4 Pest control b) Where details of processing aids are disclosed, these shall
G Bibliography
a) An effective, documented and reviewed pest control program not be changed without customer agreement.
shall be implemented and maintained to provide maximum
c) Steam boiler water additives shall be documented and not
protection from entry of rodents, animals, birds, crawling or flying
carried over, directly or indirectly, to the product.
insects and other pests, into manufacturing and storage areas.
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e) Repair and maintenance operations shall not present any hazard

d) Compressed air and gases used in processing, which come to the quality of products. Maintenance operations shall not
into contact with the product, shall be clean and free from introduce contamination and, on completion, shall include a
Home particulates and lubricants. Their quality shall be determined documented cleanliness check.
and controlled.
How to use this document f) Defective quality critical equipment shall be removed from
Contents e) Intermediate materials shall also be identified and subject to service and/or clearly labelled and product produced evaluated
Foreword
the above controls, as appropriate. (see 8.2.4). Prior to reintroduction it shall be verified as suitable
Acknowledgements f) All utilities, e.g. air, gases, steam, water, shall be subject to a for use.
documented risk assessment for their potential impact on the g) The organization shall ensure the infrastructure is managed,
0 Introduction quality of the packaging materials and any associated risks. operated, cleaned and, where appropriate, maintained in
Records of the assessment shall be maintained accordance with GMP to avoid product contamination, including
1 Scope
(see 4.2.4). validation of the cleaning procedures, control of particulate
2 Normative reference g) Appropriate ventilation and exhaust systems shall be matter and microbiological control where applicable.
provided, where necessary, to minimize contamination. h) The organization shall define and document a cleaning schedule
3 Terms and definitions Particular attention shall be given to recirculation systems. that takes into account the contamination risk.
Quality management h) If water comes into direct contact with the packaging material, it’s i) Where it is essential to use brushes and/or compressed air for
4
system starting material or is used for cleaning the equipment in contact cleaning production equipment and working areas, their use
with the product, its quality shall be determined and controlled. shall be controlled to avoid the risk of contamination.
Guidance
Cleaning schedules should include manufacturing, storage and administration
7 Product realization Guidance areas covering aspects such as floors, doors, walls, ceilings, light fixtures,
Dependent on the risks, the use of food-grade fluids should be considered. sinks and exposed pipes.
Measurement, analysis Documented procedures and schedules for cleaning should define where
8 Risk assessments should include anti set-off powder and fluids, e.g. lubrication
and improvement
fluids, cooling fluids, hydraulic oils. applicable:
Guidance on risk
A • cleaning methods
management
Guidance on verification 6.5 Maintenance and cleaning activities • materials used, e.g. detergents/disinfectants
B • areas/equipment to be cleaned
and validation requirements a) The organization shall establish documented requirements and
• precautions and spillage cleaning routines
C Barcodes schedules for maintenance activities, e.g. production processes,
• records required
systems and equipment, where such activities or lack of, may
Following cleaning, equipment should be stored in a clean and dry condition
D Cleanrooms affect product quality.
and separately from soiled equipment.
b) Maintenance shall be recorded (see 4.2.4).
c) Computerized systems that may impact upon material quality
Supplier Certification shall have sufficient controls for installation, operation,
F
Scheme
maintenance, modification and security (see GAMP).
G Bibliography d) The organization shall maintain a set of technical documentation
for quality critical equipment and installations.
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7. Product realization Guidance

Organizations supplying secondary packaging components, especially
Home printed or other higher risk components, should also be encouraged
How to use this document to ensure that risk management processes form part of planning and
Contents implementation throughout product realization (see Annex A).
Foreword
7.1 Planning of product realization
Acknowledgements 7.2 Customer-related processes
a) Processes required for product realization shall be planned and
0 Introduction developed. There shall be consistency between the planning of 7.2.1 Determination of requirements related to the
product realization and other processes within the QMS product
1 Scope (see 4.1). The organization shall determine the product specification
b) The organization shall determine the following: including the quality, labelling and delivery requirements of the
customer, including product statutory and regulatory requirements.
• product classification, e.g. primary, secondary, OINDP/ Requirements not stated by the customer but necessary for specified
3 Terms and definitions complex materials, origination/artwork or intended use, where known, shall be considered (see 7.2.1.2).
Quality management • documents, product requirements, quality objectives and
4
system resources needed for product realization 7.2.1.1 Customer product component codes
• attributes and testing required specific to the product, which a) The organization shall understand how its individual customers
shall include verification, validation, monitoring and inspection allocate and revise component codes in order to ensure the
and the criteria for product acceptance systems of both the organization and its customers interface
• records to demonstrate the realization process and resulting effectively.
7 Product realization product meets requirements (see 4.2.4)
b) The organization shall have a documented process for the
Measurement, analysis verification of electronic data output (see 7.5.2.1).
8
and improvement c) The organization shall ensure that risk management
processes are included in the planning and implemented
Guidance on risk
A throughout product realization (see Annex A).
management
B
and validation requirements Each resulting requirement from this planning shall be consistent
and suitable for the organization’s method of operations.
C Barcodes
Guidance
D Cleanrooms Documents specifying the processes of the quality management system
(including the product realization processes) can be referred to as a quality plan.
The organization should consider applying the requirements given in 7.3 during
Supplier Certification the development of product realization processes.
F
Scheme
G Bibliography
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7.2.1.2 Specifications 7.2.1.3 Additional requirements

The organization shall establish documented specifications to Additional requirements, whether customer-specific, legal or
Home
define the product(s) to be supplied. regulatory, e.g. pharmacopoeial material and general monographs,
How to use this document Guidance shall be agreed by both parties (see 7.2.1 and 7.2.3.2).
Contents The following categories relating to product quality should be considered for Requirements and changes related to the product shall be
Foreword inclusion in the specification, where applicable, for example: determined and documented.
• product name
Acknowledgements
• product reference code Guidance
0 Introduction • product dimensions and limits Technical/quality agreements should form the basis of determining both
• product performance, i.e. functionality, for example: customer and organization responsibilities including the actions to be taken
1 Scope - leakage in the event of a nonconformity. In the absence of such agreements, the
- spray pattern organization should consider generating their own (see 7.2.3.2).
2 Normative reference • raw material, when applicable:
- chemical requirements 7.2.2 Review of requirements related to the product
- mechanical properties a) The organization shall review the requirements associated
4
Quality management - biological properties with the order and any changes thereafter, before supply
system - storage commences, e.g. submission of tenders, request for information,
5 Management responsibility - grade order/contract, and that the requirements have been clearly
- supplier defined, understood and communicated to ensure product
6 Resource management • product cleanliness standard: compliance.
- foreign particulates level b) Where requirements are not clearly stated and documented
7 Product realization - microbial level by the customer, the organization shall confirm agreed
- BSE/TSE compliance statement requirements prior to order acceptance.
8 • visual standards
and improvement
c) The organization shall ensure variances are resolved prior to
Guidance on risk • sampling plans
A commencement of the order/contract.
management • testing methods
Guidance on verification • acceptance criteria, e.g. acceptable quality levels/limits (AQLs) d) The organization shall have the facilities, resources and
B process capability to consistently meet the mutually agreed
and validation requirements • extractables
• product certification, e.g. certificate of analysis (CoA), certificate of specifications.
C Barcodes
conformance (CoC), or certificate of testing (CoT) e) The output from reviews, including activities arising, shall be
D Cleanrooms • packaging details recorded and maintained (see 4.2.4).
• label details
E Drug Master Files (DMF) • pallet details
7.2.3 Customer communication
• storage conditions and shelf-life setting a) There shall be provision for providing accurate and pertinent
F
Scheme • product use-by date/requalification date communication to the customer. Provision should be made for
• transportation details replying to customer enquiries, contracts and order handling
G Bibliography requirements.
b) Customer feedback and complaints shall be documented
(see 7.2.3.1 and 8.2.1).
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c) The organization shall agree with the customer those changes 7.2.3.2 Supply agreements, quality agreements and
which need to have documented prior approval and those documentation
changes which need to be notified (see 7.5.1.14).
Home
d) The organization shall certify products to the required Guidance
How to use this document specification, in accordance with or as required by the customer. It is recommended that the organization and customers should establish supply
Contents
agreements and quality agreements. Supply agreements may cover issues not
e) A documented feedback system shall be established by the related to quality, e.g. commercial issues such as pricing, terms of agreement,
Foreword organization to provide early warning of potential and actual other legal clauses, environmental policies, etc. These should be subject to
Acknowledgements quality problems as well as facilitating customer input into the periodic review.
corrective and preventive action process (see 8.5.2 and 8.5.3). Quality agreements should agree to the terms relating to key quality and
0 Introduction regulatory systems.
7.2.3.1 Complaints The following categories should be considered for inclusion in quality
1 Scope agreements, where applicable:
a) The organization shall have a documented procedure outlining
• organization and customer responsibility matrix
2 Normative reference the activities associated with a quality complaint
• definitions
(see 8.3 and 8.5.2).
• batch records
3 Terms and definitions b) The organization shall: • deviations/resolutions of quality issues
Quality management • maintain an official record of all complaints and their status in • change control and notification:
4 - document change control
system the system
- material change control
5 Management responsibility • notify appropriate internal departments of the complaint - specification change control
• investigate complaints in a timely manner - process change control, and
6 Resource management • have a mechanism for investigating complaints, tracking the - facility and equipment change control
progress of the investigation, and responding to the customer • cleanliness and hygiene
7 Product realization on the outcome of the investigation and corrective actions • complaints and impact on commercial supply
• maintain records of complaints, together with their • product testing
8
and improvement
investigation and actions taken (see 4.2.4) • customer audits
• document retention
Guidance on risk c) A summary of complaints, including trends shall be included in
A • lot approval and product release
management the management review process.
• manufacturing environment
Guidance on verification d) Quality complaints not followed by corrective and/or preventive • material suppliers
B
and validation requirements action shall be justified and also recorded (see 4.2.4). • process validation
C Barcodes • qualification and/or validation of equipment
• recalls
D Cleanrooms • reference to current versions of standards and guidelines
• regulatory compliance
E Drug Master Files (DMF) • regulatory contacts and audits
• requirements for raw materials and subcomponents
Supplier Certification • retained samples
F
Scheme • customer samples; these may include a representation
G Bibliography of each printed station or moulding cavity
• rework and reprocess
• subcontractor management
• supply agreements
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e) There shall be a documented procedure for design and

Item Customer Organization
development. As part of the planning process, the organization
Component Specifications X shall evaluate and document any potential risks of the product
Home Specifications against which material is tested X and design and determine the relevant aspects of GMP which
How to use this document by the organization may impact on the customer and ultimately the patient.
Contents Supply/procurement projections X
Foreword Testing in-process/release X
Acknowledgements f) The organization shall develop a process to understand
Testing on receipt X critical requirements to address customer specific application,
0 Introduction Certification CoA, CoC or CoT X i.e. quality critical attributes so as to help them select the
Retained samples X correct product.
1 Scope X
Supply agreement X X g) The organization shall interface with the customer to
2 Normative reference determine and demonstrate the fitness for use of the product
Quality agreement X X
with respect to performance features.
Design file X X
h) The product(s) shall be demonstrated to function correctly and
Quality management
Table 1. Responsibility Matrix Example maintain stability with respect to the design features defined
4 by the customer or as applicable throughout the shelf-life.
system For items where the organization and the customer have joint responsibility,
5 Management responsibility the customer has ultimate responsibility.
6 Resource management 7.3 Design and development Guidance

7.3.1 Design and development planning Identification of potential risks and mitigation of those risks is a key
responsibility of the organization.
a) The organization shall plan and control all stages of design and
Measurement, analysis The purpose of risk assessment is to identify potential risks, evaluate the effect
8
and improvement development for its products.
of those risks, together with defining and implementing preventive actions to
Guidance on risk b) The organization shall determine the following: mitigate their potential impact.
A
management There should be agreement between the customer and the organization on
• the stages that incorporate design and development
Guidance on verification responsibility for design and risk assessment.
B
• the appropriate review, verification and validation activities for
each stage of design and development The design and development outputs should be verified as suitable before the
C Barcodes • the relevant responsibilities and authorities required for design production specifications are finalized.
and development One method of fulfilling this may be to supply a product requirement
D Cleanrooms questionnaire that can be completed by the customer and reviewed by the
c) Where there are different groups involved in design and organization as an initial step in identifying components for evaluation. Another
E Drug Master Files (DMF) development, the organization shall manage the interfaces method would be for the customer to define a ‘User Requirement Specification’
between these groups to ensure clear assignment of (URS) see 3.84. The organization would transfer this into a ‘Functional
F
Scheme
responsibility and effective communication. Specification’ (FS) to deliver the technical solution, including process controls.
d) As design and development progresses the planning output shall Features to be considered include, but not limited to:
G Bibliography • suitability of intended use of end product
be updated, as appropriate.
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• use of appropriate and standardized test methods and application of 7.3.1.2 Process Analytical Technology (PAT)
appropriate acceptance criteria to ensure product is stable during intended G Length Width Length Width
Home
use conditions by the customer Guidance
• compatibility of the product with the intended drug formulation components The organization is encouraged but not required to become familiar with the
How to use this document over time principles of process analytical technology (PAT) and to implement it, where
Upper Tuck Flap
Shoulder
Contents • product use-by/recertification date, recommended storage conditions, and appropriate and possible, into its manufacturing processes.
Foreword associated tests, methods and acceptance criteria The goal of PAT Top Closure
isPanel
to understand and Dust control the manufacturing Dust process, W+T/2
Flap Flap
Acknowledgements thereby producing a more consistent product of higher quality.
7.3.1.1 Material use-by/requalification date The organization should ensure that its manufacturing processes, quality
0 Introduction control, and documentation systems are at a high level of quality before
During design and development the organization shall interface
with the customer to establish the following: implementing PAT.
1 Scope
The foundation of PATRear is a firm understanding ofFront
the manufacturing
Right process.
Glue Flap
Left
• product ‘use-by’ or ‘requalification’ date and recommended
Implementation of Panel Side Panel Side Depth
PAT entails understanding the critical parameters
2 Normative reference storage conditions as evaluated under a defined set of
Panel Panel
of a product and their relationship to the critical control points in the

conditions to understand product behaviour
3 Terms and definitions manufacturing process which ensure that those parameters are within
• packaging and over-wrap of product to protect against
specification.
Quality management environmental contaminants
4 PAT also involves implementing in-process controls and testing, and
Set Back
system • relevant recognized standard test methods, where available,
encourages continual improvement. Dust Dust
capable of measuring typical characteristics of the product Flap Bottom Closure Flap
5 Management responsibility The benefits of PAT include higher quality product, Panelless end-product testing,
increased efficiency, and fewer reject or re-processed batches. Shoulder

Lower Tuck Flap
6 Resource management Organizations interested in implementing PAT should consult with their
• a detailed description of tests, methods and acceptance customers for additional guidance.
7 Product realization criteria for component functionality
• use of appropriate and standardized test methods in addition to
Measurement, analysis the application of appropriate acceptance criteria to ensure the
8
and improvement
product meets key incoming inspection and test criteria and is 7.3.2 Design and development inputs
Guidance on risk stable during warehouse storage, distribution and handling
A a) Inputs which relate to the product requirements shall be
management
• technical information for performance testing of product determined. These records shall be maintained (see 4.2.4) and
B
and validation requirements under typical use conditions shall exist and be appropriate to include:
the design
C Barcodes • requirements for performance and function
• studies that characterize differences in product behaviour
• any regulatory and statutory requirements
under exposed conditions of accelerated temperature,
D Cleanrooms • information from other similar designs, where applicable
pressure, cold, light, stress, strain, as appropriate, in order
• all other essential requirements for design and development
to define the optimum storage condition and shelf-life of the
E Drug Master Files (DMF) product b) There shall be a review of these inputs for adequacy.
Supplier Certification The requirements shall not conflict with each other, be
F unambiguous and shall be complete.
Scheme
G Bibliography c) Due to the nature of supplying the pharmaceutical industry there

is a level of regulatory expectation. This shall take the form of
one or more inputs depending on the supplied market
(see 7.3.2.1).
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7.3.3 Design and development outputs

7.3.2.1 Marketing Authorisation
Documented outputs shall be provided in a manner which allows
a) Samples and certification documents provided for the organization and the customer to perform verification to prove
Home evaluation, stability testing or clinical trials for Marketing that the resulting output meets the input requirements. Design and
How to use this document Authorisation applications, shall be compliant with the same development outputs shall:
Contents GMP procedures and controls as a normal production item,
• meet the input requirements (see 7.3.2)
Foreword and with the same traceability. Material composition and
• include appropriate information to enable purchasing,
processing conditions shall be equivalent to those which production and service provision
Acknowledgements
apply during routine commercial manufacture of the item. • reference the product acceptance criteria
0 Introduction • specify the characteristics of the product that are key for its
b) As part of a Marketing Authorisation application, the
customer may require the organization to provide specified safe and proper use
1 Scope
information. An appropriately qualified individual within the
organization shall approve such information.
7.3.4 Design and development review
a) Systematic design and development reviews shall be completed
Examples of such information are:
and documented at selected milestones in the development
• composition process as planned (see 7.3.1). These reviews are required to:
Quality management • test data • evaluate the results of the design and development and the
4
system • specifications ability of these results to meet requirements
5 Management responsibility • control methods • identify any problems and propose required actions
• processing conditions
b) The review shall include a cross-functional team representing
6 Resource management c) Alternatively, and to facilitate organization confidentiality, the different disciplines involved in the design and development
scientific and technical information may be supplied as a of the product. Records of the results and any subsequent
7 Product realization dossier directly to the regulatory authorities, for example actions shall be maintained (see 4.2.4).
Measurement, analysis in the form of a Drug Master File (DMF), or European
8
and improvement Pharmacopoeia Certificate of Suitability, in connection with 7.3.5 Design and development verification
Guidance on risk the application for a Marketing Authorisation. a) Verification consists of testing performed on the product to
A
management ensure the design and development outputs have met the design
d) Records shall be maintained (see 4.2.4) of information
B
Guidance on verification supplied to customers or regulatory authorities. and development input requirements. It shall be performed in
and validation requirements accordance with the plan (see 7.3.1). Records of the results of
e) Changes that affect any of the data supplied by the the verification shall be maintained (see 4.2.4) and include any
C Barcodes organization shall be communicated to the customer or the necessary actions.
regulatory authority (see 7.2.3 and 7.5.1.7).
D Cleanrooms b) Samples of product resulting from new or modified designs shall be:
Guidance • fully tested and analysed against the product specification
E Drug Master Files (DMF) Key changes may involve a customer having to perform a stability and • customer approved
Supplier Certification compatibility retesting programme and resubmission to the regulatory • retained as reference samples
F authorities, with final approval required to proceed with the change; this
Scheme
process may take 12 months or more.
G Bibliography
Back Forward
7.3.6 Design and development validation Guidance

a) Validation consists of testing and documenting the testing Design and development outputs can include records, e.g. specifications,
performed on the product to ensure the product consistently manufacturing procedures, engineering drawings, engineering or research
Home
meets the requirements for the specified application or intended logbooks and samples.
How to use this document Confidential scientific and technical information of the organization can be
use, where known. It shall be performed in accordance with the
Contents plan (see 7.3.1). Records of the results of the validation shall be supplied as a dossier directly to the regulatory authorities, e.g. technical
Foreword maintained (see 4.2.4) and include any necessary actions. dossier and/or master file.
Acknowledgements b) Where required, validation documentation shall be provided to 7.4 Purchasing
and approved by the customer.
0 Introduction
c) The customer shall be notified where full validation is not 7.4.1 Purchasing process
1 Scope completed prior to delivery or production of the product. a) Purchasing processes shall be defined and implemented such
that the purchased products meet the needs and requirements
2 Normative reference Guidance of the organization, including conformance to purchasing
The requirements for design and development validation should be agreed specifications.
3 Terms and definitions between the organization and the customer (see 7.2.3.2).
b) Suppliers shall be evaluated and selected based on their
4
Quality management 7.3.7 Control of design and development changes capability to supply required products/services and suppliers of
system quality critical components or services shall be approved by the
a) Changes to the component design shall be identified and
5 Management responsibility records maintained (see 7.5.1.14 and 4.2.4). quality unit (see 5.5.3 and 5.5.4).
b) The changes shall be reviewed, verified, validated, and c) Periodic review of suppliers shall be part of the QMS.
approved before implementation including retraining of d) The supplier evaluation process, subsequent actions and
7 Product realization personnel, where appropriate. ongoing reviews shall be based on the level of risk and
c) Review of design and development changes shall include documented, e.g. use of a questionnaire, approved supplier
Measurement, analysis list, site visit. The organization shall identify and seek written
8 evaluation of the effect of the changes on constituent parts and
and improvement
product already delivered. approval from the customer for any subcontracted or outsourced
Guidance on risk part of the production process. Where a process is outsourced
A
management d) Records of the results of the review of changes shall be or subcontracted the organization shall ensure that, during the
B
Guidance on verification maintained (see 4.2.4) and include any necessary actions. process, applicable GMP requirements are implemented.
7.3.7.1 Notification e) Suppliers include all contracted-out services that can affect
C Barcodes
Where a change affects any of the data supplied to the customer, product quality.
D Cleanrooms the customer shall be notified. The organization shall be responsible
for notifying the appropriate authorities where a technical dossier or
E Drug Master Files (DMF) master file has been submitted by the organization
(see 7.2.3 and 7.5.1.14).
F
Scheme
7.3.7.2 Design change
G Bibliography During implementation of a change the existing validation and
documents affected by the change shall be reviewed and revised,
and personnel shall be retrained, as appropriate (see 7.5.2).
Back Forward
f) The organization shall only use suppliers that have been evaluated 7.4.2 Purchasing information
and accepted as competent, these include but are not limited to:
a) Description of purchased product shall include, where
• origination appropriate the requirements for:
Home
• preventive and breakdown maintenance
How to use this document • the approval of product, procedures, processes and equipment
• calibration services
Contents
• personnel qualification
• laboratory services
• the quality management system
Foreword • qualification services
Acknowledgements • haulage b) For the purpose of traceability given in 7.5.3, the organization
• cleaning shall maintain the relevant purchasing information, i.e.
0 Introduction • pest control documents (see 4.2.3) and records (see 4.2.4).
• waste contractors
1 Scope
• sterilization services (see 7.5.1.1 b and 7.5.2) 7.4.3 Verification of purchased product
• consultants advising on the production and control of a) Requirements shall be established and maintained for all
packaging materials materials used. Incoming materials shall be inspected or
3 Terms and definitions g) Where consultants are utilised to advise on the production and otherwise verified as conforming to specified requirements.
control of packaging materials they shall be considered as suppliers. b) Incoming materials shall be physically or administratively
Quality management
4 quarantined until they have been approved for use through an
system h) Changing the source of quality critical raw materials shall be
subjected to change control (see 7.5.1.14). established and implemented inspection protocol (see 8.2.4.2).
5 Management responsibility Records of this verification shall be maintained (see 4.2.4).
6 Resource management 7.4.1.1 Control of supply chain c) Where sampling of the purchased product for verification
The organization shall adequately assess the criticality of the is performed, it shall be conducted in accordance with an
7 Product realization materials received from suppliers used in the manufacture of a approved sampling process designed to avoid contamination.
finished product. d) Where verification of purchased product is performed at the
8 Guidance supplier’s location, the purchasing information shall include the
and improvement
Guidance on risk Involvement of the supplier in the development of processes and verification arrangements and method of product release.
A
management specifications is necessary because the supplier of the product has a detailed
knowledge of the component. Guidance
B In exceptional circumstances, subject to a risk assessment, quarantined
and validation requirements There is an expectation for certain primary packaging products, e.g. inhalation
or sterile products that control of materials is maintained to a high level. purchased products may be used in further manufacturing provided the finished
C Barcodes product remains within the control of the organization until the approval of the
Most products of this nature involve multiple raw materials, supplied by other
organizations, i.e. suppliers who provide components directly to the customer. purchased product is confirmed.
D Cleanrooms
The organization typically sources these materials from other suppliers. It is
E Drug Master Files (DMF) expected that adequate control of raw materials by each level of suppliers
throughout the supply chain is maintained, as appropriate.
F
Scheme
Adequate control of raw materials may be determined by, e.g. a risk
assessment. This is to ensure that the appropriate controls are applied
G Bibliography by the organization with their suppliers where the materials can affect the
functionality and quality of the product supplied.
(See PQG Guide to Supply Chain Risk Management)
Back Forward
• management of the recording and documentation of process

7.4.4 Supplier data verification activities and product controls
The organization shall periodically verify the relevant and • definition and provision of procedures for investigation of
Home critical information received from their suppliers on a certificate process and product deviations, including problem solving
How to use this document of analysis (CoA), certificate of conformity (CoC), or certificate and prevention, waste reduction, process optimisation and
Contents of testing (CoT). improvement
Foreword c) All quality critical deviations shall be investigated and the
Guidance
Acknowledgements outcome shall be recorded (see 4.2.4).
This may mean performing similar testing on site, by an independent
0 Introduction contractor, or routine audit of the facilities to ensure that there is a high 7.5.1.1 Cleanliness of product and contamination
level of confidence in the supplier information. controls
1 Scope In lieu of such testing by the organization, a report of analysis, e.g. CoA,
CoC, or CoT, may be accepted from the supplier, provided that at least 7.5.1.2 General
2 Normative reference one specific identity test is conducted on the material or sub-component There shall be documented standards or specifications,
by the organization. The organization should also establish the reliability of procedures and controls to ensure the following:
3 Terms and definitions the supplier’s analyses through appropriate validation of the supplier’s test
• cleanliness of packaging material to prevent contamination
results at appropriate intervals.
4
Quality management of equipment or product
system • all production and controlled areas are operating within
5 Management responsibility 7.5 Production and service provision specified conditions, including environmental controls
• production processes in controlled environmental conditions
7.5.1 Control of production and service provision where required by the customer
a) Production activities and provision of services shall be carried • cleaning of equipment used for the production of packaging
7 Product realization out under controlled conditions. This shall include assurance materials; records of the cleaning of equipment critical to the
of the compliance of the product or service to the customer quality of the production shall be maintained (see 4.2.4)
Measurement, analysis requirements, as well as continual improvement of the product • the cleanliness status of all areas/production equipment is
8
and improvement and efficiency of processes. identified
Guidance on risk
A
management b) Activities that shall be controlled include, but are not limited to: • reprocessing of material shall be defined and agreed with the
• provision of appropriate specifications and information that customer
B
and validation requirements define the product and shall include the definition of the date
• reground thermoplastic materials shall not be used unless agreed
of manufacture
C Barcodes with the customer
• definition and provision of appropriate manufacturing
• risks to patient safety shall be evaluated e.g. Transmissible
equipment, including operating process parameters and
D Cleanrooms Spongiform Encephalopathies (TSE)
operating procedures
• definition and provision of appropriate measuring and • agreed requirements when a primary packaging material is
E Drug Master Files (DMF) cleaned by the organization prior to sterilization, where the
monitoring equipment, including operating procedures,
Supplier Certification measurement intervals and sample sizes cleanliness of a primary packaging material is of significance in
F
Scheme • provision of procedures for processes and activities, where use, or during manufacture where process aids are to be removed
their absence could impact quality • identification of storage containers and associated attendant
G Bibliography
• definition and provision of procedures and criteria for approval manifolds, filling and discharge lines
of in-process, product packing and labelling, product release, • discharges in and out of bulk containers/silos have appropriate
delivery and post-delivery activities attention including identification, security and cleanliness
Back Forward
• on completion of each production run each line, equipment,

7.5.1.3 Particular requirements for sterile primary machine and/or associated work area shall be subject to a
packaging materials recorded line-clearance, ensuring that all starting materials,
Home products, samples, waste and documentation, not required for
How to use this document There shall be documented records (see 4.2.4) of the the next production run, e.g. common components, have been
Contents sterilization process and the process parameters that were used removed
for each sterilization batch. Each batch of primary packaging • where the use of common components cannot facilitate a full
Foreword
material shall be traceable to the sterilization records. line-clearance, e.g. inks, plates, varnish, tooling, this shall be
Acknowledgements
recorded as part of the line-clearance process
0 Introduction • where there is any routine temporary break (e.g. meal breaks,
7.5.1.4 Segregation controls end of shift or at weekends) in production, the processing
1 Scope a) Materials and products which cannot be segregated by physical equipment, processing area and materials shall be secured to
barriers shall be protected by other means, e.g. taped top sheet, avoid cross-contamination
2 Normative reference stretch/shrink wraps, covers, nets or enclosed cages, to avoid • where a batch is ‘lifted’ part way through a process
risk of cross-contamination. operation (i.e. temporarily removed, with the expectation
3 Terms and definitions of reintroduction at a future time or date, e.g. breakdown/
b) The processing of products with similar appearance, e.g. design,
Quality management shape, colour, in close proximity to each other shall be avoided part production), the subsequent material shall be identified
4 and documented as for a new batch, before returning to the
system to reduce the risk of cross-contamination.
production run
5 Management responsibility c) If this cannot be avoided, additional precautions based on the
evaluation of risk shall be taken to protect the product from 7.5.1.6 Changeover systems
6 Resource management cross-contamination. a) Changeover systems that are designed to reduce make-ready
time and do not permit a total line-clearance, shall be subject
7 Product realization 7.5.1.5 Line-clearance to a documented risk assessment and operated with controls to
Measurement, analysis a) In line with the product or service supplied, the organization ensure product security.
8
and improvement
shall define the process of line-clearance to prevent the risk of b) Print media and other tooling, e.g. cutting dies, from the previous
Guidance on risk cross-contamination (mix-ups). job, shall be removed from the line prior to formal approval of the
A
management
b) During origination/artwork, the work area shall be subject run being given; this check shall be recorded (see 4.2.4).
B to a recorded line-clearance ensuring samples, proofs and
and validation requirements 7.5.1.7 Quarantine and destruction
documentation have been removed and those artwork files on
C Barcodes a) The organization shall have a documented procedure for
the computer have been closed.
quarantine and destruction which ensures:
D Cleanrooms c) During manufacture the minimum process for line-clearance
shall be: • appropriate and clear segregation controls are in place
E Drug Master Files (DMF) for product undergoing quarantine evaluation, including its
• prior to the commencement of production an independent, identification and status
Supplier Certification recorded check shall be carried out to confirm the line, • the provision of a controlled area where items are stored or
F
Scheme equipment, machine and/or associated work area are free held pending disposition arrangements (see 7.5.1.8 and 8.3)
G Bibliography
from the risk of cross-contamination (mix-ups) and that it is • that origination and print media, for a design(s) undergoing
fit for use (this may include electronic or physically applied revision, are subject to formal quarantine
variable data) • the method(s) for rendering unusable and disposing of unwanted
and superseded origination and print impression media
Back Forward
Guidance • defines naming conventions, folder structures and the

Quarantine area controls may include the provision of a secure area, disposition of rejected, obsolete and archive origination/
e.g. locked for high value or market sensitive products in line with customer artwork files
Home • defines a system of origination version control to ensure only
requirements/agreements.
How to use this document the relevant version of origination/artwork is used
Contents 7.5.1.8 Waste material
Foreword
7.5.1.10 Product security
a) Secure waste-disposal practices shall be enforced to avoid
Security codes general
Acknowledgements risk of counterfeit products reaching the market. The most
appropriate method of waste disposal shall take into account a) To ensure the security of the product and prevent cross-
0 Introduction
suitable environmental and secure recycling options. contamination, security codes (see Annex C), shall be included
in the profile of pharmaceutical printed packaging materials,
1 Scope b) The handling of waste material shall be controlled to prevent the
where practicable, for verification either by the organization
risk of cross-contamination and unauthorized use. This also aids
2 Normative reference during manufacture, and/or by the customer during the packing
reconciliation.
operation.
c) The organization shall be responsible for ensuring the secure
b) For cartons and other board products, each type and variety
disposal of all waste or scrap material. This may include but not
shall include a unique security code incorporated into the profile.
4
Quality management be limited to product artwork, print media, samples, process
system defectives and waste materials. c) Any product produced which deviates from specified electronic
5 Management responsibility inspection, shall be properly authorized and recorded in the
d) All waste or scrap material shall be securely contained, clearly
quality records. The customer shall be notified and documented
identified and removed from processing and storage areas
6 Resource management approval obtained before product release.
pending disposal in accordance with a documented procedure.
d) Where security codes are included by the organization, the
7 Product realization 7.5.1.9 Origination/artwork organization shall document a policy for the allocation and
Measurement, analysis a) Origination material both physical and digital shall be uniquely control of the codes and maintain a register of issued codes
8
and improvement
identified and stored in secure environments (see 4.2.3.1). (see 4.2.4).
Guidance on risk
A b) Origination processing areas shall be subject to a documented Guidance
management
Guidance on verification procedure for contamination control that: Where the organization is responsible for specifying the security code, each
B colour of the artwork should be included in the code.
and validation requirements • defines work areas
• specifies one job at a time Security codes should be unique for each new version of a component.
C Barcodes
• details a documented line-clearance (see 7.5.1.5 b) For all barcodes, if a colour is not compatible with the requirements of the
• ensures security of materials relating to the job scanning equipment, this should be notified to the customer.
D Cleanrooms
Verification codes, e.g. glue flap, converters and crease codes may be located
c) Digital origination shall be subject to a documented procedure on part of the profile or component, which is subsequently concealed or
that: removed, e.g when the carton is formed/erected or removed.
Supplier Certification • details line-clearance including the requirement that all Codes used for verification should be inspected or electronically verified at
F
Scheme
origination files on the active computer have been closed appropriate operations as part of the process, e.g. critical control points such
G Bibliography (see 7.5.1.5 b) as origination, plate-making and in-process checks.
• establishes a secure, validated, file access system designed to
prevent unintentional use of incorrect origination/artwork files
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Converter’s flap code

a) The organization shall agree with the customer any converter Guidance
flap codes contained within the profile of the product, to assist in Print media should be stored in an environment suitable to maintain its
Home
the prevention of admixtures. integrity.
b) Where included a register of all converter’s flap codes shall be b) Plate management
Contents
maintained (see 4.2.4).
Foreword • where semi or automatic plate making facilities are used,
c) The converter’s flap code shall be visually inspected and verified which result in collated multiple plate set output, there
Acknowledgements at appropriate converting operations. shall be a documented risk assessment and controls
0 Introduction implemented to mitigate the risk of cross-contamination of
Guidance
artwork designs/plate sets
The converter’s flap code may be located on a part of the design which is
1 Scope • where more than one printing plate is required, there shall
subsequently covered when the carton is erected, e.g. on the inner edge of the
be a documented procedure for ensuring that all plates
2 Normative reference tuck in flap.
within the set are used
Crease codes (edge codes) • where a set of plates contains the generic design for
3 Terms and definitions several jobs, there shall be a documented procedure
a) Where the product artwork incorporates crease codes, the codes
Quality management shall be visually checked during the packing operation. defining the controls implemented to mitigate potential
4 risk of cross-contamination, including the clear unique
system
b) Where the crease codes are incorporated by the organization, a
identification of individual plates within the set(s)
5 Management responsibility register of unique codes shall be maintained (see 4.2.4) to ensure
• where a design requires several plates and some of them
clear differential between artwork versions.
are to be replaced because of a copy/design change,
Guidance there shall be a documented procedure to allow for the
7 Product realization Crease codes are generally incorporated along the folded crease, which should replacement of the affected plate(s) and the retention of the
be visible when packed into outers and used as a visual aid in the prevention of other media in the set; the original plates shall be subject
Measurement, analysis to a procedure that allows re-identification
8
and improvement
admixtures.
Guidance on risk c) Print machine set-up (initial make-ready)
A
management 7.5.1.11 Print related processes • print machine set-up (initial make-ready) shall be performed
B
Guidance on verification a) Print impression media using unprinted stock
and validation requirements • make-ready for subsequent processes may use material
• all print impression media shall be:
C Barcodes • clearly and uniquely identified so that it is traceable to the from the initial print process of the same batch
origination material • initial make-ready material may be reused during the make-
D Cleanrooms • produced from and traceable to the origination material held by ready process to achieve correct colour
the customer • material used for make-ready shall be segregated and then
E Drug Master Files (DMF) • verified against the copy approved by the customer and the disposed of as production waste
check recorded • during a production run, if replacement print media is
F • stored in a secure area with a documented procedure for required, plates shall be made from an existing fixed
Scheme
authorized issue and return to store approved source, e.g. negatives or computer-to-plate
G Bibliography • verification of the design on print impression media shall be technology from an existing stepped image
carried out during the printing machine make-ready and before • commencement of the job shall be continued after a new
the approval to produce the product is given (see 7.5.1.11 c) documented ‘first-off’ check has been carried out
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• if plates are created from a new source, e.g. restepping 7.5.1.12 Printed materials
a ‘one-up’ image the existing job shall be lifted; the
a) Leaflets
Home replacement plates shall be treated as new and
For production of leaflets, the organization shall:
How to use this document subsequent production shall be treated as a new batch
• operate a validated control system to prevent the inclusion of
Contents
• quality records shall document the introduction of all
partially printed or blank leaflets; controls may be mechanical/
replacement print media (see 4.2.4)
Foreword electronic double sheet detection, electronic print presence
Acknowledgements Guidance recognition system or a combination of both
If final inspection is a requirement, it should be completed prior to final • pack all leaflets in securely sealed outer packaging in quantities
0 Introduction
release (see 8.2.4.4). determined within tolerance limits agreed with the customer
Final inspection might not include all specification parameters. • validate the system for ensuring accuracy in counting
1 Scope
b) Reel fed materials (general)
d) Digital printing Unless otherwise specified by the customer, splices shall be:
2 Normative reference • the flexible capability of digital printing introduces • made using a brightly coloured adhesive tape on both sides
additional challenges, which shall be controlled and of the web (reverse side of backing web only for labels)
documented to ensure the accuracy and security of the • checked either side of the splice to ensure identical materials
Quality management printed products are joined
4
system • the use of digital printing and any special requirements for • the quantity of material (length, number of units or weight)
the product shall be agreed with the customer produced on each reel shall be determined within accuracy
• the organization shall establish a secure file access limits agreed with the customer and recorded on the reel
system, which is designed to prevent unintentional use of • the batch identity, reel number and production date shall be
incorrect origination files recorded on the inner face of the core for each individual reel
• unless alternative security is designed, the controlling
7 Product realization • to prevent admixtures, the web shall be run to plain material
computer in the digital printing machine shall only have the
at the end of the run to ensure no printed material remains in
8
Measurement, analysis specific artwork file in its memory for the current print run,
and improvement the printing equipment; removal and disposal of waste shall
and removal of this file shall form part of documented line-
Guidance on risk be recorded (see 4.2.4)
A clearance
management • where it is necessary to leave printed material in the
• operational settings to achieve acceptable colours shall be
Guidance on verification converting equipment - due to the difficulty in carrying out
B established through a formal process and recorded
• for reel-fed production on continuous basis there shall be a re-webbing, e.g. slitters, there shall be a formal documented
defined gap between each printed job e.g. printed dummy procedure for removing and disposing of the material used to
C Barcodes
text or blank material to ensure product separation; the pull the new design through the machine
D Cleanrooms subsequent processes shall be verified to ensure correct • the organization shall have a validated system for detecting,
separation of products and removal of defined gap material removing and segregating product produced with missing
E Drug Master Files (DMF) colours or text
e) Gang printing • the batch identity, reel number and production date shall be
Supplier Certification Gang printing (the process of printing more than one design on recorded on the inner face of the core for each individual reel
F
Scheme a substrate at one production run) is recognised and classified
• to prevent admixtures, the web shall be run to plain material
as an acute contributory risk relating to admixtures. Therefore
G Bibliography at the end of the run to ensure no printed material remains in
this shall only be permitted in agreement with the customer and
the printing equipment; removal and disposal of waste shall
on completion of a documented risk assessment to evaluate and
be recorded (see 4.2.4)
mitigate the risk of cross-contamination, (see 7.2.3.2 and 7.2.3).
Back Forward
d) A documented procedure for verification of male Braille tooling

• to prevent admixtures, the web shall be run to plain shall be established before use.
material at the end of the run to ensure no printed material
e) Braille tooling shall be maintained and its condition checked
Home remains in the printing equipment; removal and disposal of
prior to use.
How to use this document waste shall be recorded (see 4.2.4)
• where it is necessary to leave printed material in the Guidance
Contents
converting equipment - due to the difficulty in carrying References should be present on all Braille tooling and screens plus any
Foreword out re-webbing, e.g. slitters, there shall be a formal associated media, e.g. overlays used to verify Braille integrity.
Acknowledgements documented procedure for removing and disposing of the If Braille tooling is outsourced, technical specifications should be available and
0 Introduction
material used to pull the new design through the machine agreed between the organization and the tool maker/screen manufacturer.
• the organization shall have a validated system for Braille quality can be defined as correct position, orientation, format, and
1 Scope detecting, removing and segregating product produced dot height as defined and agreed in the relevant customer specification. This
with missing colours or text can be in the form either of a combination of physical or visual testing (e.g.
2 Normative reference c) Reel fed self-adhesive labels micrometer, or by suitable validated automated equipment).
• labels which are missing or have been removed from the Where changes to tooling/screens are required there should be a documented
3 Terms and definitions backing web shall not be replaced, unless the replacement procedure in place to assess the impact of change, e.g. change control/
Quality management is validated by an automated system in agreement with the validation.
4 Any such change should include a formally recorded repeat make-ready check
system customer
• where sequential numbering is incorporated, the numbering that verifies correct product quality.
See EN 15823 Packaging – Braille on packaging for medicinal products.
process shall be verified for accuracy and checked regularly
• other overprinting processes, agreed as part of the contract,
shall be subject to the same verification controls 7.5.1.14 Change control
7 Product realization d) Combination products a) When required the organization shall agree with the customer
Processing of combination products, e.g. label/leaflets, which changes require written confirmation prior to approval
8
and improvement carded leaflets or other similar assemblies, requires additional and which changes require notification only. Proposed changes
consideration. The organization shall: shall be communicated in a timely manner and the process for
Guidance on risk
A • operate systems appropriate for the secure production of each introducing changes agreed (see 7.2.3).
management
Guidance on verification of the sub-components e.g. leaflets (see 7.5.1.12.a) b) The organization shall establish and operate a documented
B
and validation requirements • operate a validated control system to ensures that every procedure for an effective change control system, incorporating
assembly is made from the correct sub-components (see 7.5.2) the evaluation of risk(s) associated with all proposed changes
C Barcodes
that can have potential impact on the quality of supplied product,
D Cleanrooms 7.5.1.13 Braille service provision and business activity.
a) Where Braille is included in the product design, there shall be a c) The detail and level of change control shall be determined by the
E Drug Master Files (DMF) formal documented procedure for ensuring the Braille text and evaluated risk in conjunction with the customer. The organization
orientation are correct and comply with the specifications for
F
Supplier Certification shall determine the impact of the change on the quality of the
Scheme size, position and embossed height.
component.
G Bibliography
b) Control systems shall include unique Braille references to
provide traceability to the original source.
c) A register of all Braille tooling shall be maintained (see 4.2.4).
Back Forward
d) The organization shall determine the impact of the change 7.5.2 Validation of processes for production and
on the quality of the component. The evaluated risk shall be service provision
assessed in accordance with the customer’s specified level
Home a) The organization shall identify validation work needed to prove
of validation requirements commensurate with the customer’s
How to use this document control of the quality critical aspects of their particular operations.
end product. Therefore it is important that the end use of
Contents the supplied product/service is fully known and understood b) Where the quality cannot be verified by subsequent monitoring or
Foreword by all parties. The evaluation shall determine if validation or measurement, control shall be demonstrated through validation,
revalidation is required. and shall be recorded (see 4.2.4).
Acknowledgements
e) The organization’s change control procedure shall ensure c) All records of validation shall be maintained for a minimum of two
0 Introduction years after retirement of the equipment, unless otherwise agreed
supporting data is generated to demonstrate that the change will
result in a product of desired quality and safety, consistent with with the customer (see 7.2.3.2).
1 Scope
the approved specifications. d) Risk assessment shall be used to determine, which processes
2 Normative reference are quality critical, and to the extent of the validation
f) An independent group shall have the responsibility and
requirements. This shall focus on, and be related to the required
authority for approval of changes. Approved changes shall be
3 Terms and definitions quality related attributes.
implemented in a controlled manner.
Quality management e) The organization shall establish documented procedures for
4 Guidance
system validation. The extent of verification and/or qualification/validation
The customer communication process should be based on product risk evaluation shall be conducted in accordance with a documented risk
and notification (see example in Table 2 below). assessment.
f) Validation of an individual primary packaging material may be
7 Product realization Product / Service Level of Risk appropriate, if required by the customer (see 7.2.3.2).
Primary Packaging Material 3 g) If a sterilization process is outsourced, the organization shall
8
and improvement Secondary Packaging Material 1, 2 or 3 ensure the process complies with the relevant clauses of this
Standard (see ISO 11135, ISO 11137, and ISO 14937).
Guidance on risk Origination/Artwork 1, 2 or 3 (dependant on category of
A
management product associated to) h) Technical systems, e.g. machines, lines, structural production
Guidance on verification Sub-contracted services 1, 2 or 3 (dependant on category of
components, used for manufacturing packaging materials,
B
product associated to) shall be verified and/or qualified/validated, in accordance with
a documented risk assessment.
C Barcodes
Level 1 The customer is to be notified of the changes. i) If sterilization is a requirement, the organization shall establish
D Cleanrooms Level 2 The customer is to be notified prior to implementation, with an agreed time documented procedures for the validation of sterilization
lag such that the customer has an opportunity to evaluate the implication for processes. Sterilization processes shall be validated prior
E Drug Master Files (DMF) their processes. to initial use. Records of the results of sterilization process
validation shall be maintained (see 4.2.4, ISO 11135 and
Supplier Certification Level 3 The customer is to be provided with the documented risk assessment
F and give acceptance of the proposed level of validation in relation to the ISO 11137).
Scheme
change prior to implementation. j) Where sterilization is a requirement, the organization shall
G Bibliography After the change has been implemented, there should be a documented subject the packaging materials to a validated sterilization
evaluation of the first three deliveries produced or tested under the change. process and record all the control parameters of the
Table 2. Quality risk determination sterilization process (see 4.2.4).
Back Forward
Guidance Examples of criteria that may result in the requirement for

Examples of activities and items requiring validation: revalidation:
• qualification of equipment, measuring and monitoring devices, including • changes to equipment, materials or processes that may alter
Home
electronic scanning equipment and software used for process control the product characteristics or quality (including software
How to use this document • materials, processes and facilities intended to assure cleanliness or sterility changes)
Contents • equipment and methods used to verify conformity and quality of the • failure to meet the required quality or adverse trends in quality
Foreword materials and products indicators
• processes critical to pack integrity • transfer of product or processes from one facility to another
Acknowledgements
occurs
0 Introduction 7.5.2.1 Validation of software provision
Guidance
1 Scope a) Validation of software used in quality critical processes shall Change control of the validation process should form part of the organization’s
include functional tests to verify the traceability, transfer change control policy.
2 Normative reference accuracy and retention of data. These tests shall be performed For guidance on verification and validation (see Annex B).
in sufficient number and under defined conditions.
3 Terms and definitions b) The software shall be challenged, e.g. by entering correct and 7.5.2.3 Verification methods/equipment
Quality management incorrect data to detect the traceability, transfer accuracy and a) Where practicable, every security barcoded item shall be
4
system retention of data or records. Results shall be recorded verified by on-line scanning equipment to ensure the codes are
(see 4.2.4). readable and that the correct product is being produced.
c) There shall be protection and security of electronic records b) The scanning equipment software/control configuration shall be
6 Resource management against accidental corruption and loss. This storage shall permit effectively controlled to prevent unauthorized tampering. Where
regeneration; if this is not possible, there shall be retention of feasible, codes shall be loaded from an independent source, e.g.
7 Product realization hard copies for two years beyond retirement of the equipment, specification or approved proof.
or as agreed with the customer.
8 c) There shall be an effective system for rejecting any product that
and improvement
Guidance fails the scanning process.
Guidance on risk
A For further details on data security, management and software validation, d) Product rejected by on-line scanning system shall be inspected
management
Guidance on verification see IEC 60601-1-4, GAMP, CFR 21 part 11, EU GMP Annex 11 & 15. to determine the cause of rejection and the rejected components
B subsequently scrapped.
C Barcodes
7.5.2.2 Revalidation of processes for production and e) Rejection findings that present a potential risk to the security of
service provision the product shall be recorded (see 4.2.4) and reviewed prior to
D Cleanrooms The organization shall establish criteria for the requirement product release.
for revalidation following significant changes (see 7.5.1.7), and f) The on-line scanning equipment and its associated reject
E Drug Master Files (DMF) where subsequent product or service deficiencies are identified mechanism shall be challenged during production to determine if
Supplier Certification during use. This may include the requirement to perform periodic its operation is effective in detecting incorrect barcoding.
F
Scheme revalidation, verification and/or qualification.
g) Such monitoring shall take place at the start of the batch, at
G Bibliography defined intervals throughout the batch, and shall be recorded
(see 4.2.4).
Back Forward
h) Any product produced where electronic scanning is specified, but f) There shall be documented procedures to ensure any materials
has not been performed, shall be authorized by the quality unit returned to the organization are distinguishable from routine
and recorded in the quality records. The customer shall be notified production and identified at all times.
Home and documented approval obtained before product release. g) The batch record shall be maintained and archived as per the
How to use this document i) Where multi-lane production code verification cannot be quality agreement or broader supply agreement (see 7.2.3.2).
Contents performed, agreement with the customer shall be documented h) The content of the CoC, CoA, or CoT shall be agreed between
Foreword to permit single or reduced lane verification. the organization and the customer (see 7.2.1.2).
Acknowledgements
Guidance
0 Introduction Scanning of security codes should be carried out during the last feasible i) The following information shall be present in the batch record
production process, e.g. folding for leaflet production. for primary packing material:
1 Scope
Where feasible both sides of a printed product should be scanned. • product name
2 Normative reference • product reference code
7.5.3 Identification and traceability • approvals
3 Terms and definitions • batch or lot number
a) The use of all production materials shall be traceable and
• dates of manufacture and release
Quality management documented from source through to product realization.
4 • use-by/requalification date
system The extent of the records required shall be based on a risk
• list of specification requirements and acceptance criteria,
assessment (see 4.2.4, and Annex A).
5 Management responsibility including AQLs
b) Unique starting material (raw material) batch numbers shall be • list of test methods
6 Resource management assigned on receipt and recorded in the batch records. Records • specification number
of process equipment used and maintenance shall be retained. • sampling plan for device or component
c) Information shall be established in batch records and shall j) The following documentation shall be available from the
Measurement, analysis include, but is not restricted to: primary packaging organization and shall be maintained and
8
and improvement archived as per the quality system:
• code, name or reference for each material, intermediate and
Guidance on risk
A
management
finished product • list of applicable validation reports
• batch number for each material, intermediate and finished • incoming quality inspection and acceptance of raw
B product materials documentation
• key dates of manufacturing activities, process steps, analyses, • master production records
C Barcodes approvals
• identification of equipment used, as well as any special
D Cleanrooms storage facilities Guidance
• applicable test methods and results, sampling plans,
E Drug Master Files (DMF) Activities should be established and planned in such a way that it facilitates the
specifications, acceptance criteria used
use of information and data for continual improvement.
Supplier Certification • product expiry date, where defined
F
Scheme For packaging starting materials, e.g. inks, coatings, adhesives and processing
d) There shall be a unique batch or identification reference for batch
aids, where the processing parameters do not allow for full and accurate
G Bibliography production records.
traceability of usage, the recording of batch numbers is not required unless it is
e) The use of quality critical equipment shall be recorded and a customer specified requirement.
records retained (see 4.2.4).
Back Forward
7.5.4 Customer property f) Where specific transport or storage conditions are required,
a) The organization shall establish a process for the management they shall be stated on the label, and these conditions shall be
of all property owned by the customer. Examples of customer complied with.
Home
property may include: g) The number of units in each transit container or shipping outer
• manufacturing equipment, e.g. mould-press tools, dies shall be determined within tolerance limits agreed with the
Contents customer and validated.
• raw materials, components supplied for inclusion in a product
Foreword
• customer samples and subsequent controlled return or
Acknowledgements disposal h) Where defined, the shelf-life shall be justified. Where material
0 Introduction • packaging materials, labels or other printed media has limited shelf-life, or requires specific storage conditions,
• electronic data files and media the organization shall ensure a system for the management of
1 Scope • intellectual property, such as drawings, specifications, this has been established and is maintained. Specific storage
documents conditions shall be controlled and recorded (see 4.2.4).
2 Normative reference b) The organization shall have a documented procedure for
identification of customer property, as well as appropriate
3 Terms and definitions Guidance
storage, handling, maintenance and use of it, in order to protect
Quality management the condition and value of the property. Consideration should be given to the need for monitoring/testing of the product
4 during storage to verify its conformity to the end of the defined shelf life.
system
c) The condition and performance of the property shall be The following minimum details should be included on transit packaging unless
5 Management responsibility monitored and recorded. If property is damaged, lost or otherwise specified by the customer:
identified to be unsuitable for use, the organization shall inform • the organization’s name and address
6 Resource management the customer promptly. • description of contents
7.5.5 Preservation of product • customer’s order number
• customer’s component reference and/or organization’s reference
a) The organization shall establish a documented procedure • pack quantity
8 to assure the preservation and conformity of product, and
and improvement • unique batch number
Guidance on risk
constituent parts of the product. This shall include definition of
A • date of manufacture
management the appropriate materials, processes and facilities for packaging,
The delivery should be accompanied by the organization’s delivery documentation,
handling, storage and delivery of the product.
B i.e. a delivery or advice note. The delivery documentation may be batch specific
and validation requirements b) The product shall be protected from extraneous matter or or cover multiple batches.
C Barcodes
contamination and clearly identified, segregated and securely The following details should be included unless otherwise specified by the
stored. customer:
D Cleanrooms c) Packaging used to protect and contain the product shall be • the organization’s name and address
clean and suitable with deliveries accompanied by appropriate • the site of manufacture
E Drug Master Files (DMF) documentation. • product description or name
Supplier Certification d) Transit packaging used for handling and storage protection shall • batch number
F • customer’s product reference number
Scheme have clear identification in a uniform position.
• customer’s order number
G Bibliography e) Any reuse of packaging containers shall ensure that previous
• batch quantity
labels are removed or defaced. Where containers are reused,
there shall be documented procedures to ensure that they are • number of delivery containers, boxes, pallets
cleaned, or verified as clean.
Back Forward
h) Calibration standards shall be traceable to recognised

Guidance International, National or Compendial standards as appropriate.
Folded cartons should be supplied packed on edge, within the outer, If these standards do not exist, the justification for the calibration
Home except where the quality of the components could be compromised. process shall be documented.
How to use this document Storage methods should ensure that vertical positioning is maintained.
i) All critical measuring and test devices shall be protected from
Contents
damage and deterioration.
Foreword
7.5.5.1 Batched production and stock holding j) Instruments and equipment not meeting established
Acknowledgements
The organization shall control the storage to ensure security specifications shall not be used and an investigation shall be
0 Introduction and integrity of the product and maintain its traceability back to conducted to determine the validity of the previous results since
manufacture and materials used. the last successful calibration.
1 Scope
k) Where automatic test equipment is used there shall be periodic
Guidance documented challenge tests.
2 Normative reference Batched production and holding of product in stock should only be practised
when contractually agreed with the customer (see 7.2.3.2). l) Data relating to the customer’s product including production
3 Terms and definitions and control data shall be made available, when required by
Quality management
7.6 Control of monitoring and measuring devices the customer, or its representative. This data shall be made
4 available to verify the production process, in-process and final
system a) Measuring and test equipment, including computerized systems,
control/test equipment are functionally adequate. This does not
identified as being quality critical shall be validated, calibrated
apply to the organization’s confidential intellectual property
and maintained, where appropriate.
(see ISO 10012).
6 Resource management b) Measuring equipment shall be adjusted or re-adjusted, to ensure
accurate results. Guidance
7 Product realization Checks of automated test equipment are used to verify the continued
c) There shall be controls in place to safeguard and prevent
functionality of the equipment and the test frequency should be based on a
8
Measurement, analysis adjustments that invalidate measured results. This includes
and improvement documented risk assessment.
in process instruments as well as test equipment used in the
A
Guidance on risk laboratory or release process. Automatic test equipment includes camera inspection systems, automatic
management weighing stations and code readers.
d) When calibrating equipment, ‘as found’ and ‘as left’ data, shall
B be recorded (see 4.2.4).
C Barcodes e) The control programme shall include the standardization or

calibration of instruments and equipment at suitable intervals in
D Cleanrooms accordance with an established documented programme.
f) The calibration status shall be verifiable by the user.
g) The calibration program shall contain specific directions,
Supplier Certification schedules, limits for accuracy and precision and provisions for
F
Scheme remedial action in the event that accuracy and/or precision limits
G Bibliography are not met.
Back Forward
8.2 Monitoring and measurement

8. Measurement analysis 8.2.1 Customer satisfaction
The organization shall determine measurement activities to assess
and improvement
Home
How to use this document customer satisfaction and actively seek customer feedback relating
Contents
to service, quality and delivery performance.
Foreword Guidance
8.1 General
Acknowledgements Such activities may include customer complaints, reject rates, on time in full
The organization shall determine, collect and analyse appropriate (OTIF), customer supplier matrix, sales reports.
0 Introduction data to demonstrate the suitability and effectiveness of the quality
management system and to evaluate where continual improvement 8.2.2 Internal audit
1 Scope of the effectiveness of the quality management system can be
a) The organization shall define a documented procedure for the
made.
2 Normative reference internal audit process, which shall monitor the effectiveness of
a) The organization shall establish and review key measures at the quality management system through a planned internal audit
3 Terms and definitions appropriate intervals for performance of quality, costs and schedule.
services to: b) Internal audits shall assess compliance, capability and
Quality management
4 • ensure conformity of the product to specification effectiveness of the quality management system to achieve the
system
• ensure conformity of the quality management system requirements of this Standard and planned arrangements.
Data collated from customer feedback, nonconforming product, c) Audits shall be scheduled on the basis of the status and
6 Resource management out of specification (OOS) investigation reports, review of importance of the activity taking into account quality critical
organization performance and other relevant sources shall be process steps necessary to deliver the service or product, and
7 Product realization the basis of this review. the outputs from previous audits and nonconformities.
Measurement, analysis b) Relevant and appropriate corrective and preventive actions d) Auditors shall remain impartial of the planned assessment area,
8 shall not audit their own activity, and shall conduct the audit in
and improvement shall be the output of the review. Senior management shall
Guidance on risk ensure an implementation plan is developed and executed. line with the defined audit criteria, scope, and methods.
A
management This shall include data generated as a result of monitoring and e) Process owner(s) shall ensure that actions identified are
Guidance on verification measurement and from other relevant sources. addressed in a timely manner to prevent escalation of observed
B
c) The analysis of data shall provide information relating to: nonconformities and their causes.
C Barcodes f) Records shall be maintained and follow up verification of actions
• customer satisfaction (see 8.2.1)
• conformity to product requirements (see 7.2.1) recorded (see 4.2.4) and monitored as part of the management
D Cleanrooms review process (see 5.6).
• characteristics and trends of processes and products including
E Drug Master Files (DMF) opportunities for preventive action 8.2.3 Monitoring and measurement of processes
• supplier performance
Supplier Certification a) The organization shall identify, implement and operate
F d) Data analysis review shall include statistical techniques and
Scheme appropriate monitoring and measurement techniques for the
methods where applicable. quality management system processes.
G Bibliography
b) These methods shall be appropriate to demonstrate the
capability of the processes to achieve planned arrangements
and to verify the processes are under control.
Back Forward
c) Periodic reviews of measurement results shall be defined and

conducted, and where results are not achieved, corrective action d) The extractable profile should be established and documented both
taken to ensure conformity. qualitatively and quantitatively under defined experimental conditions.
Home
d) The quality unit(s) shall ensure quality critical deviations are e) The documentation should include:
How to use this document investigated, resolved and recorded in a timely manner
Contents • the sampling plan
(see 4.2.4).
• type and amount of solvent
Foreword
• temperature
Acknowledgements • duration
8.2.3.1 Control of processing aids
0 Introduction • extraction method
Guidance • methods of analysis
1 Scope a) Processing aids used in the overall manufacturing process, such • supporting data
as mould-release agents and lubricants used in the manufacturing f) Solvents of various polarities should be used for initial determination
2 Normative reference process, etc. may be present on the finished component. of the profiles. Use of different solvents to maximise the extraction of
b) The organization and the customer should establish in the supply different extractables may be necessary.
agreement whether the presence of any processing aids is acceptable.
4
Quality management 8.2.3.3 Control of extractables
system c) The organization should perform routine determination of processing
aid residues on all finished components unless validation involving the Guidance
5 Management responsibility materials demonstrates that the finished components meet established
a) The organization and customer should work together to develop
criteria for processing aids.
6 Resource management component extractables testing protocols to ensure that the extractable
d) If validation demonstrates that the finished components meet profiles of the components used for commercial drug product
7 Product realization established criteria for processing aids, this should be re-verified at a manufacture remain consistent with the profiles of the components
minimum annually, or as agreed by the organization with the customer. evaluated as part of the development controlled extraction study.
8 b) Routine extractables testing is the process by which components are
and improvement
8.2.3.2 Controlled extraction studies
Guidance on risk qualitatively and quantitatively profiled for extractables acceptance
A
management Guidance criteria, or released according to established acceptance criteria.
Guidance on verification Such testing is performed to monitor the quality of components to be
B
a) One possible aspect of validation for primary packaging, e.g. OINDP
used in drug product. Details on routine extractables testing and when
components, is controlled extraction studies.
C Barcodes
to conduct such testing should be agreed with the customer. Routine
b) The purpose of the controlled extraction study is to define an extractables testing may be a way to monitor identified leachables,
acceptable extractable profile under specified test conditions; this chemicals that are of specific safety concern, or where chemical
D Cleanrooms
provides the foundation for the development of routine control methods variability may affect the function of the delivery system. This testing is
for extractables, and establishment of acceptance criteria for a raw not a substitute for suitable elastomer and polymer process controls,
material or component. which are the responsibility of the raw material supplier.
F c) Controlled extraction studies should be conducted by either the c) The organization should also provide the customer with composition
Scheme
customer or the organization, or the supplier with assistance from the information for the components in order to assist the manufacturer
G Bibliography organization for all components that will contact either the drug product, in developing and conducting extractables and leachables studies.
or the patient’s mucosa. These components will be identified by the Extractables may need to be determined without specific composition
customer or the organization. information.
Back Forward
d) Extractables testing should be performed by either the customer, or Guidance

the organization, or the supplier with assistance from the organization Safety thresholds and best practices for Extractables and Leachables
Home on those components that contact either the drug product and/or the in Orally Inhaled and Nasal Drug Products, PQRI Leachables and
How to use this document patient’s mucosa. The customer would identify these components for Extractables Working Group, Product Quality Research Institute, (2006).
Contents the organization. Recommendations
Foreword e) Components that do not contact the patient’s mouth or nasal mucosa
Acknowledgements or the drug product should be controlled by tests which are relevant to 8.2.4 Monitoring and measurement of product
their performance or functional attributes. Extractables testing of these a) The organization shall monitor and measure product quality at
0 Introduction components is not required. appropriate stages, to ensure the product consistently meets
f) Extractables testing should be conducted by the customer, the specification requirements, in accordance with a documented
1 Scope
organization, or the supplier with assistance from the organization, procedure.
and should be performed both during design and development and for
2 Normative reference b) Records (see 4.2.4) shall be maintained to demonstrate
routine release testing. This may be specified in the quality agreement.
conformity of the product and the identity of the person(s)
3 Terms and definitions g) Testing should be planned and be a part of a system of manufacturing authorising the release of the product.
controls, along with in-process controls and supplier verification.
Quality management Extractables testing on bulk materials used in a component may
4
system 8.2.4.1 Investigations of OSS results
be performed if the extractables profile of the bulk material and the
5 Management responsibility extractables profile of the component are comparable. a) The organization shall, as required by a documented procedure,
define and carry out investigation into any out of specification
h) Methods for routine extractables testing should be based on: (OOS) results.
• the analytical evaluation of the extractables identified in a controlled
b) The outcome of investigations shall be recorded (see.4.2.4).
7 Product realization extraction study during development
• the toxicological evaluation of leachables identified in the initial
Measurement, analysis 8.2.4.2 Incomming inspection and testing
8 studies on the product, which would be conducted by the customer,
and improvement a) A documented inspection and testing protocol for incoming
where possible
A
Guidance on risk materials shall be defined, which includes the methodology for
management i) The methods should be discriminatory and appropriate acceptance
criteria should be set for the extractable profile(s) for each of the approval and verification.
B incoming individual components or bulk material. b) In line with the inspection and testing protocol, the organisation
j) Specifications should be established in order to monitor for significant shall establish and maintain requirements for all materials used
C Barcodes as part of the manufacturing process.
changes as well as the appearance of new peaks in the extractables
D Cleanrooms profile.
8.2.4.3 In-process controls
k) The test methods employed in extraction studies should be documented
E Drug Master Files (DMF) and validated in accordance with current International Conference a) The organization shall, as required by documented procedures,
on Harmonisation (ICH) requirements for impurities. It is recognised define and carry out in-process controls to inspect and test the
Supplier Certification product during processing.
F that authentic materials of extractables may not be available. In
Scheme
such instances, it is acceptable to employ individual compounds as b) Additional in-process controls shall be carried out after an
G Bibliography representative of compound classes for validation studies and as equipment breakdown or an unscheduled interruption which
quantitation standards. Method performance should be assessed at or stops the process.
near the expected extractables levels.
Back Forward
c) Samples removed from the defined working area(s) shall be

stored securely until no longer required and then disposed of in 8.2.4.7 Characterisation and functionality testing
a controlled manner. They shall not be returned to the production
Home area or be incorporated into the product. a) The organization shall establish, communicate and seek
agreement from the customer, for product specifications
and testing requirements including, but not limited to, the
Contents d) Where “point of sale” codes GS 1, EAN, Code 39, PZN, data
sampling plan, the test method description and validation
Foreword matrix, etc. are incorporated into the design, a documented
requirements where appropriate, and acceptance criteria
sample verification check shall be carried out during the
Acknowledgements (see 7.2.1.2).
production process (see Annex C).
0 Introduction b) Test attributes and specifications shall address storage and
use. Those parameters requiring periodic testing prior to the
1 Scope 8.2.4.4 Final inspection
expiry date of the component shall be clearly defined and the
a) The organization shall implement an approval process for testing interval determined and agreed.
2 Normative reference authorizing release of products from the organization.
3 Terms and definitions b) Final release shall not proceed until satisfactory completion of all
planned arrangements (see 7.1), and shall be carried out in line 8.3 Control of nonconforming product
Quality management with a documented procedure.
4 a) Raw, intermediate, finished or returned suspect material or
system
c) Sample requirements and sampling methods shall be defined; media which does not conform to specification shall be clearly
5 Management responsibility their appropriateness and statistical validity understood and identified and controlled to prevent inadvertent use, application
shall be representative of the production process. or delivery.
d) Samples used in final inspection and testing shall not be b) Senior management shall ensure there are documented
7 Product realization returned to the production area or be incorporated into the procedures that define the processes in place, including details
product. of responsibilities and authorities:
8
and improvement
8.2.4.5 Retained samples • to ensure nonconforming products are put on hold to prevent
A
Guidance on risk further use or processing and are clearly identified and stored
management Retained samples taken shall be in accordance with the in a manner to prevent inadvertent use, i.e secure quarantine
Guidance on verification organization’s and/or customer requirements, clearly identified and area (see 7.5.1.7)
B
and validation requirements voided if they leave the control of the organization. • for conducting investigations and implementing actions to
C Barcodes address nonconformance
8.2.4.6 Product release • for identification of any nonconforming or associated suspect
D Cleanrooms a) A review of batch documentation shall be performed in order to material, which is remaining, or has left the control of the
release the order. organization
b) When producing to a customer specific order, overruns in • for a recall process
excess of any agreed tolerance, shall be either shipped with the • to inform the customer, where appropriate
F • that defines the process for release or concession
Scheme order or scrapped unless agreed with the customer.
arrangements ensuring any such product meets minimum
G Bibliography regulatory requirements
• documents the nature of the nonconformity, the root cause
and any corrective actions taken to minimize recurrence
Back Forward
c) When considering correction via rework or reprocessing, a b) Data sources shall include but not be limited to:
risk assessment of any adverse effect of the reworking on the • customer feedback through monitoring of satisfaction levels
Home
products shall be performed and recorded (see 4.2.4) which (see 8.2.1)
How to use this document takes into account the risk of: • product conformity reviews
Contents
• potential damage to the product • process and product trends highlighting opportunities for
Foreword • nonconforming product being missed by the sorting/reworking preventive action (see 8.5.3)
Acknowledgements operation • complaint data including internal communications
0 Introduction
• potential cross/physical contamination risks (see 7.2.3.1 and 5.5.5)
d) There shall be a documented procedure that has been approved • supplier performance and evaluation
1 Scope by the quality unit(s), which defines the organizations rework • customer and internal audits (see 5.2.1 and 8.2.2)
and/or reprocessing protocol. Where specified (see 7.2.3.2) the • key business indicators, e.g. training evaluation, process
2 Normative reference rework and/or reprocessing protocol shall be agreed with the performance
customer. c) The organization shall establish and maintain a documented
3 Terms and definitions framework for the analysis of data, to identify existing or
e) If material has been produced under cleanroom conditions, any
Quality management rework shall be carried out under the same conditions. potential causes of nonconforming product or other quality
4
system problems.
f) Following rework or reprocessing, material shall be assessed
5 Management responsibility and where required further sampling and testing (see 8.2.4) to 8.5 Improvement
demonstrate conformity to the agreed quality level requirements.
6 Resource management 8.5.1 Continual improvement
g) Unless the organization is satisfied that the product can be
sorted or otherwise reworked to remove nonconforming material a) The organization shall take a proactive approach to continually
and achieve the agreed quality level, it shall be destroyed. improve the operational and quality management system
8
Measurement, analysis processes.
and improvement Guidance
b) Senior management shall be responsible for defining a
Guidance on risk The recall procedure should be capable of being operated at any time and
A documented program of continual improvement activities,
management will take into account notification to the supply chain, stock return logistics for
appropriate review periods with approval output.
B recovery, storage of recovered product and disposal.
and validation requirements c) The organization shall identify opportunities through the use
The effectiveness of the recall procedure should be periodically evaluated.
C Barcodes Arrangements for notifying relevant stakeholders within a specified time frame of key input drivers such as the quality policy, objectives, audit
should be defined within the procedure, e.g. contact details. performance, analysis of data, customer focus, management
D Cleanrooms review, corrective actions and market initiatives.
8.4 Analysis of data d) Changes proposed as part of continual improvement shall be
E Drug Master Files (DMF) subject to a risk management process and change control where
a) The organization shall develop methods for evaluating the
Supplier Certification effectiveness of the quality management systems through applicable.
F
Scheme collective data and key indicators to analyse performance
G Bibliography and appraise opportunities for continual development and
improvement.
Back Forward
8.5.2 Corrective action Guidance

a) The organization shall establish and maintain a documented The use of Failure Mode & Effects Analysis (FMEA), risk analysis, analytical tools,
procedure to define the actions agreed and implemented as a trends, and inputs from monitoring and measuring should be considerations in
Home
result of nonconformities arising. the process adopted.
How to use this document Preventive actions should be considered a proactive approach to business and
Contents
b) The scope of corrective actions assigned to any nonconformity
process improvement.
shall be determined by the criticality and effect of the
Foreword
nonconformity.
Acknowledgements
c) The organization shall define the process for:
0 Introduction
• reviewing nonconformities arising including customer
complaints (see 7.2.3.1), and outputs from first, second and
1 Scope
third party audits
2 Normative reference • the method(s) for establishing the causes of nonconformities
and process for implementing required action(s)
3 Terms and definitions • follow up evaluation to determine the effectiveness of the
action(s) implemented to ensure the risk of recurrence is
Quality management mitigated
4
system
• recording results of action(s) taken (see 4.2.4)
5 Management responsibility • the evaluation of corrective action(s) taken
6 Resource management Guidance

Corrective action should also be a key consideration input into the organization’s
7 Product realization continual improvement development and risk management process.
Measurement, analysis 8.5.3 Preventive action
8
and improvement
Guidance on risk a) The organization shall establish and maintain a documented
A procedure to define the organizational approach, tools and
management
Guidance on verification methods for preventive actions.
B
b) The scope of preventive actions shall be determined by the
C Barcodes extent and effect of the potential problem(s).
c) The organization shall define the process for:
D Cleanrooms
• identifying prospective nonconformities, their causes, and
E Drug Master Files (DMF) evaluation of actions to mitigate risk to prevent occurrence
• establishing, developing and implementing agreed action(s)
F needed
Scheme
• recording results of action(s) taken (see 4.2.4)
G Bibliography • the system for evaluation of preventive action(s) taken
Back Forward
Figure A.1 shows the steps involved in the Risk Management process. Further
Annex A (informative) information regarding the details of each of the steps can be found in the
references at the end of this Annex and the Bibliography.
Home
Guidance on risk management
Contents Initiate
Foreword Quality Risk Management Process
Risk management should be an integrated part of any business, and for
Acknowledgements successful implementation the following are key foundations:
Risk Assessment
0 Introduction • there should be top level management support and commitment
• start simply and avoid complexity Risk Identification
1 Scope • look at internal and external risks
• follow the cycle several times, learn, evolve and embed in the organization
2 Normative reference Risk Analysis
culture

Risk management can help organizations safeguard the quality and supply of
Unacceptable
product to their customers and ultimately the end user. It is about anticipating Risk Evaluation
Quality management hazards and controlling risk through an ongoing process of risk awareness,
Risk Management tools

4
Risk Communication
system reduction and/or acceptance, and review. This approach can help justify
5 Management responsibility improvement and investment where it is needed, and prevent both potential Risk Control
problems for customers, e.g. product recalls, or even patient harm and loss of
6 Resource management business. Applying the principles of risk management can provide a number of Risk Reduction
benefits, for example:
7 Product realization • improve and develop business relationships between the organization and Risk Acceptance
Measurement, analysis their customers, thereby supporting business continuity and security of
8 product supply
and improvement
Guidance on risk • reduce costs
A • minimise cost of nonconformance Output / Result of the
management
Quality Risk Management Process
Guidance on verification • improve business efficiency
B • increase confidence of customers and regulators
Risk Review
• reduce liability
C Barcodes
• increase security of supply Review Events
• avoid waste and scrap
D Cleanrooms
Appropriate risk management (see Figure A.1) should apply to both the materials
E Drug Master Files (DMF) and the manufacturing process. Two aspects of risk should be considered,
probability and consequence. How likely is the risk to occur and how severe the Figure A.1 Risk Management Overview (from ICH Q9)
F
Scheme
consequences may be.
Those involved in risk management should be representative of the relevant
G Bibliography
technical functions within the business as well as have experience in risk
management. It is management’s responsibility to ensure that the risk
management process is applied appropriately.
Back Forward
References
Further information can be obtained from the following standards/ documents:
ISO 15378:2006 Primary Packaging Materials for Medicinal Products - Particular
Home
requirements for the application of ISO 9001:2000, with reference to Good
How to use this document Manufacturing Practices (GMP)
Contents
ISO 31000:2009 - Risk management – Principles and guidelines. This standard
Foreword has been developed to meet the needs of a wide range of organizations and is a
Acknowledgements useful resource document.
0 Introduction PQG - A guide to supply chain risk management for the pharmaceutical and
medical device industries and their suppliers. The objective of this guide is to help
1 Scope reduce supply chain risk through application of the principles and tools of risk
management, and provides a common framework. This guide is freely available
2 Normative reference from the PQG and CQI websites.

ICH Q9 - Quality Risk Management. This guideline developed by ICH
(International Conference on Harmonisation) provides guideline principles and
Quality management examples of tools for quality risk management that can be applied to different
4
system
aspects of pharmaceutical quality throughout a product life cycle. It may also be
5 Management responsibility useful within the supply chain for pharmaceutical packaging materials.
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
Back Forward
The validated status of equipment and process should be maintained. Any

Annex B (informative) changes however minor should be assessed for impact on the validation status of
equipment or product and if necessary additional validation performed.
Home
Guidance on verification and Assessments should be carried out to determine if revalidation is required.
validation requirements
Quality critical equipment should be periodically revalidated to confirm its
Contents
validated status.
Foreword
Acknowledgements These notes are intended to provide a point of reference when validation is B.2 Alternative approaches to validation
0 Introduction required for defined quality critical parameters which cannot be verified from Organizations may decide which validation approach is most suitable for their
routine monitoring and measuring. requirements, through risk assessment but alternatives to prospective validation
1 Scope Validation should provide documented evidence which gives an assurance that are:
the process, when performed to predetermined parameters will consistently • concurrent validation
2 Normative reference produce a product which meets specific acceptance criteria. This also applies to • retrospective validation
software. • bracketing or matrix validation
Validation can be broken down into several stages which are planned through References
Quality management a validation master plan (VMP). All stages should be documented. A risk
4
system
Good Automated Manufacturing Practice (GAMP).
assessment should be carried out to determine the scope and purpose of the
The ISPE’s guide The Good Automated Manufacturing Practice (GAMP) Guide
5 Management responsibility validation.
for Validation of Automated Systems in Pharmaceutical Manufacture describes
a set of principles and procedures that help ensure that pharmaceutical products
6 Resource management B.1 The key stages of validation
have the required quality.
• Design Qualification (DQ) incorporating a risk analysis, User requirement
7 Product realization One of the core principles of GAMP is that quality cannot be tested into a batch
specification (URS) and contract specification. This is not necessary for
of product but must be built into each stage of the manufacturing process. As a
8
Measurement, analysis non-customised equipment unless modifications have been made
and improvement result, GAMP covers all aspects of production; from the raw materials, facility and
• Factory acceptance test (FAT): this can include environmental controls
Guidance on risk equipment to the training and hygiene of staff.
A • Installation qualification (IQ)
management • Operational qualification (OQ): this should include procedures, calibration, Standard operating procedures (SOPs) are essential for processes that can affect
Guidance on verification cleaning and training the quality of the finished product.
B
• Site acceptance test (SAT) this can include verification of calibration of The rules governing medicinal products in the European Union,
C Barcodes equipment when in situ Volume 4 - Guidelines for good manufacturing practices for medicinal products for
• Performance qualification (PQ): this is normally carried out over three runs human and veterinary use (annex 15 Qualification and validation).
D Cleanrooms to confirm reproducibility or a risk assessment carried out to justify the
amount of data gathered
All actions taken should be documented including any follow up actions.
F
Supplier Certification Validation is not complete until all steps are addressed and closed off unless a
Scheme risk assessment has been carried out detailing the reasons for acceptance before
G Bibliography completion.
Back Forward
It is possible to increase the number of available codes by using two or three rows
Annex C (informative) of code but this requires multiple scanning heads; also registration and alignment
is more critical.
Home
Barcodes Certain combinations of code and background colour do not give sufficient
contrast and will not read correctly. Highly reflective surfaces such as aluminium
Contents lidding foil can also be problematic and it may be necessary to print the barcode
Foreword on an opaque background.
C.1 Barcode types The direction of scan has to be considered. The code can be read either left
Acknowledgements
C.1.1 General to right or vice versa depending on the direction in which the code passes the
0 Introduction scanning head.
Different types of barcoding systems are employed in the pharmaceutical
1 Scope industry, for example: This symbology does not include any check digit or auto-discriminatory (start/
stop) bars.
• security codes defined, originated and controlled in one organization)
2 Normative reference • communication codes used by more than one organization in the supply C.3.2 Interleaved two of five (ITF) codes
chain to accurately capture data electronically
3 Terms and definitions This is based on ITF symbology and can encode all or part of a numeric
These barcodes allow visual or electronic identification of items. component code. Start/stop bars are included to show orientation. There is a
Quality management
4 check digit (Modulo 10).
system
C.2 Security codes
Because of the interleaved nature of this code (digits are paired and for each pair,
5 Management responsibility The use of a barcode system is complementary not alternative to other the first digit gives bars whilst the second defines the spaces), it is very compact
procedures for the avoidance of admixtures. These codes can be printed in inks and, subject to checks on scanning equipment, can encode as many as 18
transparent to the human eye (and therefore can be used over other text) and can characters in 25mm using a thin bar of 0.19mm and a wide:narrow ratio of 2.2:1
be scanned by UV light readers. (the minimum recommended).
It is best used with a constant and even number of numerical characters.
8
Measurement, analysis C.3 Barcode systems
and improvement
The following barcode systems are used by the pharmaceutical industry. C.3.3 Code 39 (also described as Code 3 of 9)
Guidance on risk
A
management This can encode all or part of an alphanumeric code: the complete alphabet,
C.3.1 Pharmacode figures and some punctuation symbols. It is also possible to encode all128 ASCII
B The most common symbology (also known as the Laetus code) consists of thin
and validation requirements characters, using precedence codes.
and thick bars separated by white spaces. Thick bars are usually three times the Every code 39 character has five bars and four spaces and these nine elements
C Barcodes
width of thin bars and the space between bars is twice the width of thin bars. are also defined with three wide and six narrow elements (hence 3 of 9 or
D Cleanrooms Provided this ratio is maintained, there is some flexibility in bar widths and hence Code 39).
the overall lengths of codes but thin bars are usually in the range of 0.4mm to Germany PZN (Pharma Zentrale Nummer), Italy and Portugal all require Code 39
E Drug Master Files (DMF) 0.7mm. barcodes on cartons. Code 39 has also been used in some warehousing, QA and
Supplier Certification Miniature codes may be used where there is little space available with thin bars dispensary operations.
F
Scheme (down to 0.35mm and spaces down to 0.65mm), but reduction below these Code 39 is self-checking and is not normally used with a check digit but
G Bibliography
dimensions is not advised. Each code also requires an area free from text or other an optional Modulo 43 character is required in certain applications. For the
printing either side of the code. The number of different codes depends on the pharmaceutical industry, this is important for any packs supplied to the U.S.A.
number of digits in the code. Therefore, for four digits there are only 16 possible since both the Department of Defence and the Health Industry Bar Code Council
codes whereas if there is room for eight digits, 256 different codes are available. (HIBCC) require the National Stock Number to be encoded with a check digit.
Back Forward
C.3.4 Code 128 Data Matrix is composed of two separate parts (see Figure C.3): the L shaped
finder pattern, which is used by the scanner to locate the symbol, and the
An alternative alphanumeric code which was introduced in 1981.The encoding
encoded data itself.
Home
patterns cover the full 128-character ASCII set. Each character contains three
bars and three spaces in an overall length of 11 modules. Alphanumeric data is encoded in both the height and width of the symbol in a
How to use this document series of dark or light “cells” or modules based upon a pre-determined size. The
Contents
Module one is always a bar and module 11 is always a space. It is a very high
minimum size of these “cells” is known as the X-dimension.
density code and may be of variable length so any number of characters can
Foreword The finder pattern defines the shape (square or rectangle), the size, X-dimension
be encoded. For pharmaceutical products supplied to France, this symbology is
Acknowledgements used on the peelable vignette labels which are removed from the pack as proof of and the number of rows and columns in the symbol. The other two sides from
0 Introduction dispensing and hence reimbursement. the finder pattern are alternating light and dark ‘cells’ or modules, known as the
‘Clock Track’ (see Figure C.3). This defines the basic structure of the symbol and
1 Scope C.3.5 Crease codes can also help determine its size and distortion.
Crease codes consist of bars printed in defined positions on the crease or fold of
2 Normative reference the component e.g. cartons or leaflets. This system permits the visual scanning
Finder Pattern
of the product whilst in a flat state or when packed with the creased or folded end
3 Terms and definitions uppermost. Clock Track
Quality management The crease code is visible as continuous lines down the edge of the product and
4 Data Matrix
system
a break in continuity indicates the presence of an admixture.
C.3.6 Two-dimensional (2D) Matrix barcode
6 Resource management Figure C.3 Data Matrix barcode
Two-dimensional (2D) or Data Matrix e.g. Snowflake codes, consisting of dark
and light ‘cells’ or modules arranged in either a square (see Figure C.1) or Similar to linear (1D) barcodes Data Matrix has a mandatory Quiet Zone. This is a
rectangular (see Figure C.2) pattern, occupy far less space and may contain light, text or other printing free, area around the symbol.
Measurement, analysis significantly more data than linear (1D) barcodes. The square form is the most
8
and improvement commonly used and enables the encoding of the largest amount of data; however, C.3.7 Alternative Two-dimensional barcodes
Guidance on risk the rectangle form may be selected as it is more suited to some high speed
A
management Quick Response (QR) Code (see Figure C.4)
printing techniques. 2D barcodes do require special radial readers.
Guidance on verification This code has three positioning boxes situated in the top right, top left and bottom
B
and validation requirements left corners, replacing the finder pattern, this allows for high speed decoding.
C Barcodes
D Cleanrooms

F Figure C.1 Square 2D Matrix barcode Figure C.2 Rectangular 2D Matrix barcode
Scheme
G Bibliography Figure C.4
Back Forward
Maxicode (see Figure C.5) Further details about the symbology, dimensional specifications, tolerances and
This code has a central bull’s-eye locator, replacing the finder pattern, designed positioning of the code on pack are in the GS 1 Operating Manual.
for quick high speed scanning. The Universal Product Code (UPC) used in USA. was the fore-runner of GS 1
Home
and only uses 12 digits. All UPC codes may be considered as a sub-set of
How to use this document GS 1 (converted to GS 1 by adding a leading zero) and will read on GS 1
Contents scanning equipment.
Foreword
Acknowledgements C.4.2 Traded unit codes
They are derived from a unique GS 1 number, but a leading ‘zero’ is added (to
0 Introduction Figure C.5
give 14 digits) and encoded using Interleaved ITF-14 symbology. They are used
in warehousing and distribution operations and are either printed on trays or
1 Scope C.3.8 Alternative security codes
corrugated shipping outers containing multiples of sales items, or on labels affixed
Optical character recognition (OCR) and optical character verification (OCV) can to them.
be used to verify a suitable reference such as a component code.
3 Terms and definitions Glass ampoules may include ceramic ring codes. They enable product C.4.3 Other communication codes
identification during sterilization and inspection operations and before labels are With the agreement of the trading partners, any symbology, e.g. Code 39,
Quality management
4 applied. It is possible to use up to three rings and around eight different colours Code 128, may be used.
system
but care is needed to ensure rings are far enough apart to fit the scanning
5 Management responsibility Other symbologies that are relevant to the pharmaceutical industry are:
‘window’.
a) Codabar
6 Resource management C.4 Communication codes The National Blood Service of the UK use Codabar for product codes and expiry
7 Product realization These enable automatic capture of data (usually the unique identity of the dates, and Code 128 for the unique donation number identity.
product) and are used throughout warehousing, distribution and sales. All the There are 20 different Codabar characters and these include the letters A, B, C
Measurement, analysis information regarding price or special offers is held by the computer and is
8 and D only, plus some punctuation symbols.
and improvement
‘looked-up’ when the code is scanned.
Guidance on risk b) Modified Plessey Code or MSI Data Corporation Code
A
management
C.4.1 Global Standards 1 (GS 1) - update from This is required for Code Nationale in Belgium. It is also used for marking shelves
B
and validation requirements European Article Number (EAN) to allow scanning by portable devices for inventory recording.
This is by far the most common symbology, especially at point-of-sale, and
C Barcodes C.4.4 Others
uniquely identifies the product.
Many other symbologies have been developed to fit the requirements of certain
D Cleanrooms Two series of codes are available having either 8 or 13 digits. The bars are of four
industries but are not used for pharmaceutical products. The following list is not
different widths and the minimum size of the code or magnification and orientation
exhaustive, but indicates some of these codes
E Drug Master Files (DMF) is determined by the method of printing.
a) Code 93
Supplier Certification Scanning is usually by fixed point laser, raster scan, hand held laser gun or wand.
F
Scheme Truncation (reduction in bar height) is not recommended if a high percentage This is a supplementary code to Code 39 and both symbologies can be read on
of ‘first-time-reads’ is required. Since these devices use red light, there is a auto-discriminating equipment. It is the most dense symbology for alphanumeric
G Bibliography
restriction on colours of codes and backgrounds. coding.
All bars of the code must be in the same colour in order to comply with
dimensional tolerances.
Back Forward
b) Code 49
This consists of two to eight parallel rows of code with four ‘words’ in each row. It
is used for small containers and in various transport/distribution operations.
Home
How to use this document c) Code 2 of 5
Contents Not the ‘interleaved’ version. Uses include warehouse sorting systems, photo
Foreword finishing envelopes and airline tickets.
Acknowledgements d) Code 11
0 Introduction This is a very high density, discrete, numeric-symbology, extensively used in

labelling and tracking telecommunications components and equipment.
1 Scope e) Matrix 2 of 5
A variation of Code 11 devised by Nieaf in the Netherlands.
f) Nixdorf Code
The original symbology for department store systems, largely replaced by GS 1
Quality management and ITF-14.
4
system
g) Ames Code
5 Management responsibility Used in the USA by the Medical Records System. Structure is similar to Codabar.
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
Back Forward
C.5 Barcode layout on products

Key
Home Security - automatic
1. Seven bar Pharmacode
Contents 2. Added colour bar
Foreword 3. ‘Sentinel’ bar to trigger scanner
Acknowledgements 4. Areas free from text for ‘lead-in’ and ‘lead-out’
0 Introduction
Information
5. Purchaser’s component code
1 Scope 6. Areas on trailing edge for variable data - EXP, BN and MFD 7
Communication
7. GS 1 barcode (shown here at magnification of 90%)
NOTE: Correct orientation for consumer scanning
Product X For oral administration only
5 012345 678917 >

Use only as directed by a
Quality management if label is affixed to a round bottle: code axis parallel to physician
4 Generic/active
system axis of bottle. Read leaflet before use
5mg Each tablet contains
5 mg of generic
Excipients include lactose 6
6 Resource management POM Pl0001/1234
ABC Pharmaceuticals Limited
7 Product realization Anytown, Anywhere.
100 Tablets
Measurement, analysis 55241
8
and improvement
Guidance on risk
A
management
B
4
C Barcodes
D Cleanrooms 4 1 2 3 5

F
Scheme
G Bibliography
Figure C.6 Example of codes on a pharmaceutical label

Back Forward

Key
Home Security – automatic
How to use this document 1
1, 2 and 3, are all possible positions for a Pharmacode.
Contents The final choice will depend on:
Foreword • are leaflets supplied on reels, as flat sheets or pre-folded
Acknowledgements • the direction of feed and position of scanning head
• whether both printer and user need to scan
0 Introduction • where possible, it is recommended that the final fold allows the product Patient Product Information
name to be visible 2 Product X
1 Scope Generic/active
When position 3 is required, e.g. on a pre-folded and cassetted leaflet, care is
needed on paper quality, grammage and design to prevent any ‘show-through’ 5mg
2 Normative reference 6
from text on the reverse face giving spurious images. It may be necessary to
3 Terms and definitions include a print-free ‘window’ area on the reverse. 3
Quality management 4. If reel-fed, an indexing mark is required for the cut length
4
system 1. TRADE NAME OF THE MEDICINAL PRODUCT
Information Generic 5.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
5 Management responsibility 5. Purchaser’s component code Each Product X tablet contains generic
6. Purchaser’s crease code Ph. Eur. 5mg.
6 Resource management 3. PHARMACEUTICAL FORM
Tablet. White, circular biconvex tablet,
imprinted with 5 on the obverse and plain
7 Product realization on the reverse.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
8 Product X is an anti-Xxxxxx agent.
and improvement It is indicated in all conditions where
Guidance on risk reduction of xxxxxx function
A is required. A preparation for....
management
4.2 Posology and method of administration
Guidance on verification Adults
B
and validation requirements The initial dose is in the range 10-20 mg,
taken as two to three divided doses.
This is continued until the patient is....
C Barcodes
4
D Cleanrooms
E Drug Master Files (DMF) 55342 5
F
Scheme
G Bibliography
Figure C.7 Example of codes on a pharmaceutical leafleta

Back Forward

Key
Home Security - automatic
1. Converter’s security barcode in glue flap (may include colours). 2 3 6 8 4
Contents 2. Purchaser’s barcode (may include colours or two coding rows).
Foreword Security - manual
Acknowledgements
3. Purchaser’s crease code.
0 Introduction 4. Purchaser’s crease code.
NOTE 3 and 4 above may be the same but different codes assist if cartons can
1 Scope
be reversed in magazine or cartonner.
55423
2 Normative reference 5. Converter’s flap code
Information
6. Purchaser’s component code.
Quality management 7. Converter’s station number on multiple print sheet.
4
system
8. Braille Matrix.
5 Management responsibility Communication
5 012345 678917 >

6 Resource management 9. Purchaser’s GS 1 (shown here at magnification of 90%).
9
8
and improvement
Guidance on risk 1
A
management
B
and validation requirements 10 11 12
13 14 15
C Barcodes
D Cleanrooms

Supplier Certification 7 5
F
Scheme
G Bibliography
Figure C.8 Example of codes on a pharmaceutical carton

Back Forward

Key
Home Security – automatic 4
1. Seven bar Pharmacode.
Contents
Information
Foreword
2. Purchaser’s component code.
Acknowledgements
3. Area on crimp for variable data - EXP, BN and MFD.
0 Introduction Other
1
1 Scope 4. Registration mark.
55544 2
2 Normative reference 3
4
Quality management Product X For topical administration
system only
Generic/active Use only as directed by a
5%w/w physician
8
and improvement
Guidance on risk
A
management
B
C Barcodes
POM
D Cleanrooms
PL0001/1234
ABC Pharmaceuticals Limited
xg Anytown, Anywhere.
F
Scheme
G Bibliography
Figure C.9 Example of codes on a pharmaceutical tube

Back Forward
k) Operators shall wear the following dedicated, non-fibre/

Annex D (normative) particulate shedding clothing: tunic tops and trousers or one
piece equivalent, headgear, overshoes (or area specific shoes),
Home
Cleanrooms as well as moustache/beard snoods, gloves (non-talcum
lubricated) and goggles where appropriate.
Contents
Foreword D.2 Enhanced cleanroom conditions
D.1 Standard cleanroom conditions
Acknowledgements Further enhancements and additions to the standard
These conditions are appropriate where the customer requires cleanroom conditions shall be employed where the primary
0 Introduction packaging materials for clean (but not sterile) application and shall packaging materials will either be sterilized before or after
be additional to the minimum environmental conditions where: customer use.
1 Scope
a) The organization shall define the cleanroom classification based a) Microbial contamination and material/product bio-burden test
2 Normative reference on customer requirements, e.g. ISO 14644-1. monitoring shall be performed and results recorded. Ambient
b) Compliance with the defined classification shall be ensured through conditions, of temperature and humidity, shall be controlled
3 Terms and definitions monitoring, recording and, where appropriate, use of alarm systems. to minimize bio-burden.
4
Quality management c) Aspects that shall be covered include particulate levels in the b) All protective clothing used in the cleanroom, shall be
system controlled area, air changes in the controlled area and pressure cleaned under controlled conditions. Where product is
5 Management responsibility differentials between controlled and non-controlled environments. directly exposed within the cleanroom, operators shall wear
d) Operation, support and maintenance activities shall not protective face masks.
6 Resource management compromise compliance to the classified requirements. c) Where product is cleaned after manufacture and prior to
e) Loading of raw materials to equipment used in the manufacturing subsequent assembly or packaging:
process is permitted in areas compliant with minimum • cleaning materials (e.g. water), shall be agreed with the
Measurement, analysis environmental conditions, provided they are segregated customer, controlled, e.g. including bio-burden tests, and not
8
and improvement
physically, or by air pressure differentials, from the cleanroom. introduce contaminants or leave residues
Guidance on risk
A f) Areas where primary packaging materials are subsequently • special cleaning (e.g. using an approved solvent) shall be
management
Guidance on verification assembled, inspected and packed shall comply with the same similarly controlled
B
and validation requirements classification as in a). • where cleaning is also designed to remove processing aids
C Barcodes g) Where it is a customer requirement, effective methods of (e.g. solvents used to remove processing aids), and checks
disinfection and decontamination of equipment used for are required to ensure their complete removal and the
D Cleanrooms fabrication, assembly and packaging shall be used. cleaning procedure shall be validated
h) Wooden and other fibre shedding pallets shall not be used in the • air for product drying shall be filtered to at least the same
cleanroom. standard as the cleanroom environment
Supplier Certification i) Entry into the cleanroom shall be via pressure-controlled • localised protection zones shall be equal to the cleanroom
F
Scheme
changing rooms. classification or be one grade more exacting
G Bibliography
j) Materials/products shall be transferred into and out of the
cleanroom in a manner that does not compromise the cleanroom
standard, e.g. use of interlocking doors/conveyor transfer system.
Back Forward
Guidance
Classification of clean areas/cleanrooms
Home
Clean areas/cleanrooms should be classified according to ISO 14644-1,
How to use this document and monitored/operated according to ISO 14644-2, ISO 14644-3 and
Contents ISO 14644-5 or equivalent.
Foreword For cleanroom design, construction and start-up see ISO 14644-4.
Acknowledgements Monitoring may be conducted in accordance with ISO 14698-1 and
ISO 14698-2.
0 Introduction
1 Scope
Quality management
4
system
8
and improvement
Guidance on risk
A
management
B
C Barcodes
D Cleanrooms

F
Scheme
G Bibliography
Back Forward
Annex E (informative)
Home
Drug Master Files (DMF) E.3 Benefits
The use of the DMF provides benefits for the drug product applicant, their
Contents organizations and the regulatory agencies, these benefits include:
Foreword
a) Providing for the easy access and review of detailed information
Acknowledgements regarding the component or material, e.g. physical description, intended
0 Introduction use, chemical composition, manufacturing processes and locations,
E.1 Drug Master Files (DMFs) raw material types and grades, suitability, and other administrative
1 Scope a) Organizations are not obliged to submit a DMF; this is simply a useful tool information, because all of this information is contained within a single
The
for coordination withinformation
customers and U.S.on this
Food page
and Drug Administration The
document in the information
FDA’s on this
possession. In addition, pageannual updates/
because
2 Normative reference is only
(FDA) and other regulatory applicable
agencies (see Websitefor
references for is only
amendments are required fromapplicable
DMF holders, thefor
DMF information should
information) OINDP/Complex be kept current. OINDP/Complex
b) The organization can submit aMaterial
DMF to the regulatory agency to ensure Material
b) Revealing confidential proprietary information only to the FDA, not to
Quality management that relevant information regarding an organization’s competence is made the end-user. The DMF system allows organizations to protect any
4
system available to the FDA. The FDA recommends that a DMF be submitted by information which they deem confidential or proprietary or of significant
5 Management responsibility the organization in support of the customer’s Investigational New Drug (IND) competitive value, while providing FDA access to the information it
DMF. requires to evaluate applications that use the material covered by the
6 Resource management DMF.
c) Information on DMFs is provided as guidance and is for information only.
It is not a requirement of this Standard to submit DMFs for customer’s IND, Website references
New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or General descriptions of and recommendations regarding DMFs are
Measurement, analysis other regulatory filings for pharmaceutical drug product approval. contained in 21 CFR 314.420,
8
and improvement
E.2 Types of DMFs Code of Federal Regulations, Title 21, Food and Drugs; Part 20, Section 61,
Guidance on risk
A The information on this page The
Trade secrets and information
commercial on this which
or financial information page
is privileged or
management
a) Information in a DMF is confidential to the organization and the regulatory confidential.
B
Guidance on verification isDMF,
agencies. In a typical onlythe applicable
organization shouldforidentify both proprietary is only applicable for
OINDP/Complex
and non-proprietary information that is needed to support their customer’s Guideline for Drug Master Files, CDER,
OINDP/Complex
DMF types are defined in the
Material FDA, 1989
C Barcodes filing. The DMF type should also be identified. For OINDP components, the Material
most relevant DMF types are Type III for packaging components, and Type Container Closure Systems for Packaging Human Drugs and Biologics,
D Cleanrooms V for FDA accepted reference information. CDER/CBER, FDA, May 1999
E Drug Master Files (DMF) b) Once the DMF type has been identified, the organization should consult the Guideline for Drug Master Files, CDER, FDA, 1989
associated specific DMF guidance’s for direction in preparing their DMF,
Supplier Certification e.g. Container Closure Systems for Packaging Human Drugs and Biologics
F
Scheme
(Type III), Guideline for Drug Master Files (general requirements).
G Bibliography
Back Forward
E.4 Requirements for DMF holders

The DMF holder should:
Home
a) Ensure that the content of the DMF is accurate and supported by
documentation.
Contents
b) Format the DMF, in accordance with existing guidelines at the time of
Foreword
submission, so as to facilitate ease of review.
Acknowledgements
c) Have a documented system in place to ensure annual update of the DMF.
0 Introduction
d) Have a document change control system to ensure that changes to any
1 Scope
item described in its DMF, e.g. processes, raw materials, packaging
components,The information on
subcontractors/outsource this page
organization’s, are communicated
2 Normative reference to the DMF administrator
is only applicable for DMF.
and reflected in updates to the
e) Have a customer notification system in place to ensure that changes to
OINDP/Complex
3 Terms and definitions the sections of the DMF relevant to the applicants are communicated to
Material
Quality management the applicants.
4
system
E.5 Subcontracting
Primary packaging or OINDP organizations (with a DMF) that subcontract a
6 Resource management component of their process should consider having their subcontract organization
submit a DMF. If it is not feasible for the subcontractor to submit and maintain a
7 Product realization DMF, the organization should obtain the required information through the use of
confidentiality agreements or some other contractual agreement. This should be
8
and improvement
part of the contract along with a mutual agreement on what type(s) of changes
require notification. Precise definitions of ‘change’ will help remove subjective
Guidance on risk
A interpretations byThe information
the subcontractor onchanges
of internal this thatpageneed notification.
management
Guidance on verification is only applicable for
B
and validation requirements E.6 Letters of Authorisation for FDA to refer to DMFs
OINDP/Complex
Letters of Authorisation (LoAs) to the FDA allow reviewers to clearly
C Barcodes Material
understand which portions of a DMF contain the relevant information
D Cleanrooms pertaining to the component or material of interest. This allows for more
timely and efficient review of the multiple DMFs normally referenced within a
E Drug Master Files (DMF) single filing.
A copy of the LoA should be provided to the customer.
F
Scheme
G Bibliography
Back Forward
F.1 Requirements for CQI/PQG certified supplier status

Annex F (normative) F.1.1 The organization
Home PS 9000:2011 CQI/PQG Pharmaceutical The organization (pharmaceutical supplier company/certification
body client) shall:
How to use this document Supplier Certification Scheme
Contents a) Set up its quality system and procedures to meet the
Foreword requirements of a PS 9000 Standard.
Acknowledgements b) Seek certification to the PS 9000 certification scheme from a
PQG recognized accredited certification body.
0 Introduction CQI/PQG
Develop and publish PS 9000 Standards c) Maintain its quality system and procedures to meet the above
1 Scope Publish PS 9000 Certification Scheme rules requirements.
Design and Publish PS 9000 training course criteria
CQI/PQG QMS + PS 9000 auditor certification d) Supply copies of third party certification body audit reports
2 Normative reference PS 9000 Certified Supplier recognition (initial, surveillance and re-certification audits) as requested by
PS 9000 Certification Scheme accreditation and surveillance customers and the PQG.
e) If appropriate, participate in meetings and make proposals for
Quality management CQI/PQG Accreditation CQI/PQG & IRCA improving the PS 9000 certification scheme.
4
system PS 9000 Certification Scheme IRCA QMS + PQG PS 9000
accreditation and surveillance auditor f) If appropriate, provide feedback on the PS 9000 certification
5 Management responsibility Publish training criteria and scheme’s effectiveness.
monitor course providers
6 Resource management F.1.2 The International Register of Certificated
Pharmaceutical Suppliers
Organizations supplying
Accredited certification Auditors Auditors (IRCA)
pharmaceutical
bodies (3rd party) CQI/PQG IRCA QMS
companies - obtain QMS +
Use IRCA QMS + + PQG PS 9000 auditors
IRCA shall publish the requirements for training courses for QMS +
Measurement, analysis PS 9000 certification
8
and improvement PQG PS 9000 auditors Comply with PS 9000 auditors/lead auditors.
Comply with PS 9000 PQG PS 9000 Certification
Guidance on risk Manufacture and supply
Certification Scheme rules Scheme rules
See IRCA website: www.irca.org
A Issue certificates of analysis/
management Issue QMS + PS 9000 Perform audits
conformance
B
Guidance on verification Certificates F.1.3 The auditor
The auditor (third party certification audits) shall:
C Barcodes a) Meet the PS 9000 certification scheme requirements and
Pharmaceutical Companies
Purchase and receive register with IRCA as a QMS and PQG as a PS 9000 auditor/
D Cleanrooms Provide feedback Information & feedback lead auditor.
E Drug Master Files (DMF) b) Ensure experience/familiarity with the technology of the
pharmaceutical supplier organization concerned.
F c) Ensure experience in, and understanding of, the requirements of
Scheme
Figure F.1 PS 9000 Responsibilities flowchart the pharmaceutical industry particularly the GMP requirements
G Bibliography associated and relevant to a particular material and/or
component.
Back Forward
d) Carry out audits in a professional manner according to the IRCA e) Seek clarification/advice from the PQG as necessary.
Code of Conduct. f) Participate, as appropriate, in the development of the PS 9000
e) Include positive attributes and opportunities for improvement certification scheme.
Home
using ISO 9000:2005 quality management principles, as g) Provide feedback on the PS 9000 certification scheme’s
How to use this document appropriate, in audit reports. effectiveness.
Contents
f) Seek clarification and advice, as required, from the PQG. h) Issue certificates referring to PS 9000 in the scope of an UKAS
Foreword
g) As appropriate, participate in meetings and make suggestions or equivalent accredited Certificate or as the Standard in a non-
Acknowledgements
for improving the PS 9000 certification scheme. accredited Certificate.
0 Introduction h) As appropriate, provide feedback on the PS 9000 certification i) Notify the PQG of new companies certificated to/withdrawn from
scheme’s effectiveness. PS 9000.
1 Scope
F.1.4 The accredited certification body F.2 PS 9000 Registration/certification requirements
The accredited certification body shall: F.2.1 The accredited certification body
3 Terms and definitions a) Sign an agreement with CQI/PQG to meet the PS 9000 The accredited certification body shall:
Quality management certification scheme requirements including.
4 a) Issue certificates referring to PS 9000 using the full title(s) and
system • all certification audits (initial, transition, surveillance/periodic issue reference.
5 Management responsibility and re-certification audits) shall be carried out by one of the
b) Provide copies of certificates, including appendices, to the CQI/
QMS + PS 9000 certification auditors/lead auditors on the PQG as and when certificates are issued/updated to client
6 Resource management CQI/PQG register companies.
• the GMP requirements of PS 9000 shall be examined, at every
7 Product realization audit, even if they represent only a small part of the business c) Advise CQI/PQG when new Certifications to PS 9000 have
of the supplier been issued together with the dates, duration and the name(s) of
8
Measurement, analysis the auditor(s).
and improvement • surveillance/periodic audits shall be carried out at six monthly
intervals; the period between audits shall not be greater than d) Advise CQI/PQG if certification is suspended or withdrawn
Guidance on risk
A seven months unless there are exceptional circumstances
management e) Provide an annual return of PS 9000 organizations audited to
Guidance on verification agreed with the CQI/PQG include dates, duration and name(s) of auditor(s).
B
and validation requirements b) Carry out all audits in accordance with the above requirements
C Barcodes and to the PS 9000 audit timescales; also complying with F.2.2 The CQI Pharmaceutical Quality Group (PQG)
accredited certification requirements. The PQG shall:
D Cleanrooms c) Ensure PS 9000 pharmaceutical supplier auditors are a) Administer the PS 9000 certification scheme and set up
experienced and familiar with the technology of the agreements with interested parties.
E Drug Master Files (DMF) pharmaceutical supplier company/client concerned.
b) Publish the PS 9000 pharmaceutical supplier certification
Supplier Certification d) Ensure PS 9000 pharmaceutical supplier auditors are scheme requirements.
F
Scheme
experienced in, and understand the requirements of, the
c) Develop and publish the PS 9000 pharmaceutical supplier
G Bibliography pharmaceutical industry particularly the GMP requirements
Standards.
associated and relevant to a particular material and/or
component. d) On receipt of audit certificate and auditor details verify against
the CQI/PQG register of QMS + PS 9000 certified auditors.
Back Forward
e) Issue CQI/PQG certified supplier logo origination and rules to Certificated Initial assessment Annual surveillance Re-certification /
certification bodies and certified companies. company: (auditor days) (auditor days per transition to
f) Maintain and publish the list of CQI/PQG pharmaceutical Effective annum) – audits at PS 9000:2011
Home Number of 6 monthly intervals (auditor days)
supplier certified companies.
How to use this document Personnel
g) Maintain and publish the list of CQI/PQG QMS + PS 9000
Contents
certified auditors, and
Foreword Total per
h) Carry out accreditation activities to verify that the PS 9000 Total min On-site On-site Total min On-site
Acknowledgements annum
certification scheme rules have been followed.
0 Introduction See PQG website: www.pqg.org 1–5 2.5 1.5 1.5 1 2 1
1 Scope F.3 PS 9000 Third party certification audit timescales 6 – 10 3 2 1.5 1 2 1.5
2 Normative reference The timing in Table F.1 are based on the International Accreditation 11 -15 3.5 2.5 2 1.5 2.5 2
Forum Mandatory Document for the Duration of QMS and EMS Audits
3 Terms and definitions (IAF MD 5:2009) and the consistent application of ISO/IEC 17021:2011 16 – 25 4 3 2 2 3.5 3
for audits of quality and environmental systems.The audit durations
Quality management
4
system
have been increased to allow for auditing the good manufacturing 26 – 45 5 4 2 2 4 3
practices in PS 9000:2011. In accordance with IAF guidance,
5 Management responsibility certification bodies should allow sufficient time for each audit, based 46 – 65 6 5 3 2 4.5 3.5
on the complexity of the organization and other relevant factors
6 Resource management including the language of the audit. 66 – 85 7 6 3 2 5 4
7 Product realization The total times allow for all administration, audit planning and 86 – 125 8 7 4 3 6 5
follow up.
8
and improvement Relationship between effective number of personnel and audit duration 126 – 175 9 8 4 3 6 5
Guidance on risk
A
management 176 – 275 10 8 5 4 6 5
B
and validation requirements 276 – 425 11 9 5 4 7 6
C Barcodes 426 – 625 12 10 6 5 8 7
D Cleanrooms 626 – 875 13 11 6 5 8 7
E Drug Master Files (DMF) 876 – 1,175 14 12 7 5 9 8

F
Scheme 1,176 – 1,550 15 13 7 5 10 8
G Bibliography 1,551 – 2,025 16 14 8 6 12 10
Table F.1 PS 9000 Audit duration
Back Forward
F.3.1 Surveillance and re-assessment

The guidance for initial assessment is relevant for surveillance
Home
and re-assessment. In these circumstances, where a supplier
has demonstrated to the certification/registration body during
assessment and following surveillance(s) that its quality system
Contents has reached maturity and fully conforms on a continuing basis with
Foreword all the requirements of the standard, the certification/registration
Acknowledgements body could be justified in reducing (up to a maximum of 25%) the
amount of time applied to surveillance visits and re-assessment. In
0 Introduction
such cases, where less time than that specified above is used, the
reasons shall be recorded on each occasion.
1 Scope
F.3.2 Multiple Site Certifications
Where an organization has multiple sites operating under a
3 Terms and definitions common quality system and procedures, the requirement to audit
each site every 6 months may be modified subject to documented
Quality management
4
system justification and prior agreement with the CQI/PQG.
5 Management responsibility F.3.3 Organizations with minimal PS 9000 activity

The requirement to audit each site every 6 months may be
modified subject to a mature system, documented justification and
7 Product realization prior agreement with the CQI/PQG.
8
Measurement, analysis F.3.4 Transition
and improvement
Transition auditor days are for transition from an ISO 9001:2008
Guidance on risk
A Certificate to PS 9000:2011 or for transition from PS 9000:2001 to
management
Guidance on verification PS 9000:2011
B
F.3.5 Transition from PS 9000:2001 to PS 9000:2011
C Barcodes
The audit days for transition from PS 9000:2001 to PS 9000:2011
D Cleanrooms may be reduced (up to 30%) for organizations already certified
to ISO 15378:2006. The reduction shall be justified based on the
E Drug Master Files (DMF) level of risk management and validation implemented and the
justification recorded.
F Transition from PS 9000:2001 to PS 9000:2011 shall be completed
Scheme
by 30th September 2013 after which date Certificates to
G Bibliography
PS 9000:2001 will no longer be valid.
Back Forward
Bibliography
Home
Contents
Foreword
Acknowledgements [1] BS EN ISO 9001: 2008, Quality management systems – Requirements
0 Introduction
[2] BS EN 15823:2010, Packaging. Braille on packaging for medicinal products
[3] BS 25999-2:2007, Business continuity management – Specification
1 Scope
[4] BS 31000:2009, Risk management – Principles and guidelines
2 Normative reference [5] BS 31100:2008, Risk management – Code of practice
[6] BS ISO/IEC 27001:2005, Information technology – Security techniques – Information security management systems – Requirements
[7] CFR 21 Part 211, Code of federal regulations – Title 21 – Part 211: Current good manufacturing practice for finished pharmaceuticals
Quality management
4
system [8] EN 15823 Packaging – Braille on packaging for medicinal products.
5 Management responsibility [9] Good automated manufacturing practice (GAMP) – Guide for validation of automated systems – International society for pharmacoepidemiology (ISPE) –
(http://www.ispe.org)
[10] Guide to supply chain risk management (http://www.pqg.org/publications/riskmanagement)
7 Product realization [11] ICH Q9, Quality risk management – Guidance for industry
8
Measurement, analysis [12] IEC 60601-1-4, Medical electrical equipment – Part 1-4 General requirements for safety – Collateral Standard: Programmable electrical medical systems
and improvement
Guidance on risk [13] International Accreditation Forum, IAF MD:2009 Mandatory Document For Duration of QMS and EMS Audits
A
management [14] ISO 10012-2:1997, Quality assurance for measurement equipment – Guidelines for control of measuring processes
B
and validation requirements [15] ISO 11135-1- 2007, Sterilization of health care products – Ethylene oxide – Part 1: Requirements for development, validation and routine control of
C Barcodes sterilization process for medical devices
[16] ISO 11137-1:2006, Sterilization of health care products – Radiation – Part 1: Requirements for development, validation and routine control of a sterilization
D Cleanrooms
process for medical devices
E Drug Master Files (DMF) [17] ISO 11137-2:2007, Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose
Supplier Certification [18] ISO 14644-1, Cleanrooms and associated controlled environments – Part 1: Classification of air cleanliness
F
Scheme
[19] ISO 14644-2, Cleanrooms and associated controlled environments – Part 2: Specifications for testing and monitoring to prove continued compliance with
G Bibliography ISO 14644-1
[20] ISO 14644-3, Cleanrooms and associated controlled environments – Part 3: Test Methods
Back Forward
Bibliography
Home
Contents
Foreword
Acknowledgements [21] ISO 14644-4, Cleanrooms and associated controlled environments – Part 4: Design, construction and start up
0 Introduction
[22] ISO 14644-5, Cleanrooms and associated controlled environments – Part 5: Operations
[23] ISO 14698-1:2003, Cleanrooms and associated controlled environments – Biocontamination control – Part 1: General principles and methods
1 Scope
[24] ISO 14698-2:2003, Cleanrooms and associated controlled environments – Biocontamination control – Part 2: Evaluation and interpretation of
2 Normative reference biocontamination
[25] ISO 14937:2009, Sterilization of health care products -- General requirements for characterization of a sterilizing agent and the development, validation and
routine control of a sterilization process for medical devices
Quality management
4
system [26] ISO 14971:2007, Medical devices -- Application of risk management to medical devices
5 Management responsibility [27] ISO 15378:2006, Primary packaging materials for medicinal products – Particular requirements for the application of ISO 9001:2000, with reference to
Good Manufacturing Practice (GMP)
[28] ISO 19011:2002 Guidelines for quality and/or environmental management systems auditing
7 Product realization [29] ISO 22742:2010:Packaging — Linear bar code and two-dimensional symbols for product packaging
8
Measurement, analysis [30] ISO/IEC 17021:2011 Conformity assessment - Requirements for bodies providing audit and certification of management systems
and improvement
Guidance on risk
[31] ISO/IEC 27002:2005 Information technology. Security techniques. Code of practice for information security management
A
management [32] ISO/IEC 27005:2011 Information technology. Security techniques. Information security risk management
B
and validation requirements [33] ISO/IEC Guide 51:1999, Safety aspects – Guidelines for their inclusion in Standards
C Barcodes
[34] The rules governing medicinal products in the European Union, Volume 4 - Guidelines for good manufacturing practices for medicinal products for human
and veterinary use
D Cleanrooms
E Drug Master Files (DMF) Websites

Supplier Certification Pharmaceutical Quality Group http://www.pqg.org
F
Scheme Chartered Quality Institute http://www.thecqi.org
G Bibliography Food and Drug Administration (1) http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm088828.htm
Food and Drug Administration (2) http://www.fda.gov/cder/dmf/
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5 Management responsibility Navigation

E Drug Master Files (DMF)

Acknowledgements QA review panel

E Drug Master Files (DMF)

The format of this Standard is illustrated in Figure 1.

• guidance is an integral part in this Standard and incorporated

E Drug Master Files (DMF)

Where requirements do not apply to an organization’s management

Measurement, analysis 1.2 Application

3 Terms and definitions

E Drug Master Files (DMF)

3. Terms and NOTE 2 In the case of continuous production, the batch is a

D Cleanrooms 3.3 3.7

3.36 NOTE 1 OINDP typically consist of a pharmaceutical formulation

• the intentions and approach to validation and change control

f) Changes to documentation shall be communicated to all Guidance

3 Terms and definitions

E Drug Master Files (DMF)

5.3 Quality policy

0 Introduction 5.6.1 General

6 Resource management 5.6.2 Review input

E Drug Master Files (DMF) 5.6.3 Review output

f) Maintain records including personnel education, training, skills

Guidance • changing, toilet and hand-washing facilities shall be provided

e) Repair and maintenance operations shall not present any hazard

7. Product realization Guidance

7.2.1.2 Specifications 7.2.1.3 Additional requirements

e) There shall be a documented procedure for design and

6 Resource management 7.3 Design and development Guidance

of a product and their relationship to the critical control points in the

increased efficiency, and fewer reject or re-processed batches. Shoulder

G Bibliography c) Due to the nature of supplying the pharmaceutical industry there

7.3.3 Design and development outputs

7.3.6 Design and development validation Guidance

• management of the recording and documentation of process

• on completion of each production run each line, equipment,

Guidance • defines naming conventions, folder structures and the

Converter’s flap code

d) A documented procedure for verification of male Braille tooling

Guidance Examples of criteria that may result in the requirement for

h) Calibration standards shall be traceable to recognised

C Barcodes e) The control programme shall include the standardization or

8.2 Monitoring and measurement

c) Periodic reviews of measurement results shall be defined and

d) Extractables testing should be performed by either the customer, or Guidance

c) Samples removed from the defined working area(s) shall be

8.5.2 Corrective action Guidance

6 Resource management Guidance

3 Terms and definitions

Risk Management tools

3 Terms and definitions

E Drug Master Files (DMF)

The validated status of equipment and process should be maintained. Any

G Bibliography Figure C.4

0 Introduction This is a very high density, discrete, numeric-symbology, extensively used in

E Drug Master Files (DMF)

C.5 Barcode layout on products

5 012345 678917 >

E Drug Master Files (DMF)

Figure C.6 Example of codes on a pharmaceutical label

C.5 Barcode layout on products