EN ISO 15378:2015

SLOVENSKI STANDARD
01-december-2015
1DGRPHãþD
SIST EN ISO 15378:2012
Primarni embalažni materiali za zdravila - Posebne zahteve za uporabo ISO
9001:2008 v povezavi z dobro proizvodno prakso (DPP) (ISO 15378:2015)
Primary packaging materials for medicinal products - Particular requirements for the
application of ISO 9001:2008, with reference to Good Manufacturing Practice (GMP)
(ISO 15378:2015)
Primärpackmittel für Arzneimittel - Besondere Anforderungen für die Anwendung von
ISO 9001:2008 entsprechend der Guten Herstellungspraxis (GMP) (ISO 15378:2015)
Articles de conditionnement primaire pour médicaments - Exigences particulières pour
l'application de l'ISO 9001:2008 prenant en considération les Bonnes Pratiques de
Fabrication (BPF) (ISO 15378:2015)
Ta slovenski standard je istoveten z: EN ISO 15378:2015
ICS:
03.120.10 Vodenje in zagotavljanje Quality management and
kakovosti quality assurance
11.040.01 Medicinska oprema na Medical equipment in general
splošno
55.040 0DWHULDOLLQSULSRPRþNL]D Packaging materials and
SDNLUDQMH accessories
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 15378
EUROPEAN STANDARD
NORME EUROPÉENNE
November 2015
EUROPÄISCHE NORM
ICS 11.040.01; 03.120.10 Supersedes EN ISO 15378:2011
English Version
Primary packaging materials for medicinal products -
Particular requirements for the application of ISO
9001:2008, with reference to Good Manufacturing Practice
(GMP) (ISO 15378:2015)
Articles de conditionnement primaire pour Primärpackmittel für Arzneimittel - Besondere
médicaments - Exigences particulières pour Anforderungen für die Anwendung von ISO 9001:2008
l'application de l'ISO 9001:2008 prenant en entsprechend der Guten Herstellungspraxis (GMP)
considération les Bonnes Pratiques de Fabrication (ISO 15378:2015)
(BPF) (ISO 15378:2015)
This European Standard was approved by CEN on 3 October 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 15378:2015 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 15378:2015) has been prepared by Technical Committee ISO/TC 76
"Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical
use".
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by May 2016, and conflicting national standards shall be
withdrawn at the latest by May 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document supersedes EN ISO 15378:2011.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 15378:2015 has been approved by CEN as EN ISO 15378:2015 without any modification.
INTERNATIONAL ISO
STANDARD 15378
Third edition
2015-10-01
Primary packaging materials for
medicinal products — Particular
requirements for the application of
ISO 9001:2008, with reference to Good
Manufacturing Practice (GMP)
Articles d’emballage primaire pour médicaments — Exigences
particulières pour l’application de l’ISO 9001:2008 prenant en
considération les Bonnes Pratiques de Fabrication (BPF)
Reference number
ISO 15378:2015(E)
©
ISO 2015
ISO 15378:2015(E)
© ISO 2015, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved

ISO 15378:2015(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
1.1 General . 1
1.2 Application . 2
2 Normative references . 2
3 Terms and definitions . 2
3.1 Terms relating to quality . 3
3.2 Terms relating to management . 3
3.3 Terms relating to organization . 3
3.4 Terms relating to processes and product . 4
3.5 Terms relating to characteristics . 7
3.6 Terms relating to conformity . 8
3.7 Terms relating to documentation. 9
3.8 Terms relating to examination . 9
3.9 Terms relating to risk management .11
4 Quality management system .12
4.1 General requirements .12
4.1.1 Risk management .13
4.2 Documentation requirements.14
4.2.1 General.14
4.2.2 Quality manual .15
4.2.3 Control of documents .15
4.2.4 Control of records .16
5 Management responsibility .17
5.1 Management commitment .17
5.2 Customer focus .17
5.2.1 Customer audits .17
5.3 Quality policy .17
5.4 Planning .18
5.4.1 Quality objectives .18
5.4.2 Quality management system planning .18
5.5 Responsibility, authority and communication .18
5.5.1 Responsibility and authority .18
5.5.2 Management representative .19
5.5.3 Internal communication .19
5.6 Management review .19
5.6.1 General.19
5.6.2 Review input .20
5.6.3 Review output .20
6 Resource management .20
6.1 Provision of resources .20
6.2 Human resources .21
6.2.1 General.21
6.2.2 Competence, training and awareness .21
6.3 Infrastructure .22
6.4 Work environment .22
6.4.1 Work environment requirements .22
6.4.2 Classification of clean zones/cleanrooms .23
6.4.3 Risk control of contamination .23
6.4.4 Pest control .23
6.4.5 Materials and utilities (ancillary services) .23
ISO 15378:2015(E)
6.5 Maintenance and cleaning activities.24
7 Product realization .25
7.1 Planning of product realization .25
7.2 Customer-related processes .25
7.2.1 Determination of requirements related to the product .25
7.2.2 Review of requirements related to the product .26
7.2.3 Customer communication .26
7.3 Design and development .27
7.3.1 Design and development planning .27
7.3.2 Design and development inputs .28
7.3.3 Design and development outputs .28
7.3.4 Design and development review .28
7.3.5 Design and development verification .29
7.3.6 Design and development validation .29
7.3.7 Control of design and development changes .29
7.4 Purchasing .30
7.4.1 Purchasing process .30
7.4.2 Purchasing information .31
7.4.3 Verification of purchased product .31
7.5 Production and service provision .32
7.5.1 Control of production and service provision .32
7.5.2 Validation of processes for production and service provision .34
7.5.3 Identification and traceability .35
7.5.4 Customer property .36
7.5.5 Preservation of product .36
7.6 Control of monitoring and measuring equipment .37
8 Measurement, analysis and improvement .37
8.1 General .37
8.2 Monitoring and measurement .38
8.2.1 Customer satisfaction .38
8.2.2 Internal audit .38
8.2.3 Monitoring and measurement of processes .39
8.2.4 Monitoring and measurement of product .39
8.3 Control of nonconforming product .40
8.4 Analysis of data .41
8.5 Improvement .41
8.5.1 Continual improvement .41
8.5.2 Corrective action .42
8.5.3 Preventive action .42
Annex A (normative) GMP requirements for printed primary packaging materials .43
Annex B (informative) Guidance on verification, qualification and validation requirements
for primary packaging materials .47
Annex C (informative) Relationship between clauses of this International Standard and the
high level structure .59
Bibliography .62
iv © ISO 2015 – All rights reserved

ISO 15378:2015(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 76, Transfusion, infusion and injection, and blood
processing equipment for medical and pharmaceutical use.
This third edition cancels and replaces the second edition (ISO 15378:2011), which has been
technically revised to
— include requirements on risk management and replace the former guidance on risk management by
references to relevant standards and guidelines,
— extensively revise the guidance on verification, qualification and validation requirements for
primary packaging materials, and
— amend the requirements on infrastructure, work environment, maintenance and cleaning activities,
customer communication, control of production and service provision and batch release.
ISO 15378:2015(E)
Introduction
General
This International Standard identifies Good Manufacturing Practice (GMP) principles and specifies
requirements for a quality management system applicable to primary packaging materials for medicinal
products. The realization of GMP principles in production and control of primary packaging materials
within organizations is of great importance for the safety of a patient using the medicinal product, because
of their direct product contact. The application of GMP for pharmaceutical packaging materials helps
ensure that these materials meet the needs and requirements of the pharmaceutical industry.
This International Standard is an application standard for primary packaging materials, which contains
the normative text of ISO 9001:2008.
The following are the conventions for the layout of this International Standard.
— Those clauses or subclauses that are quoted directly and unchanged from ISO 9001:2008 are in boxed text.
— Texts in italics contain additional relevant GMP information regarding primary packaging materials.
GMP terms and definitions are included in Clause 3. If listed, the source is referred to in brackets.
ISO 9001:2008, Quality management systems — Requirements
0.1  General
The adoption of a quality management system should be a strategic decision of an organization. The
design and implementation of an organization’s quality management system is influenced by
a)  its organizational environment, changes in that environment, and the risks associated with that
environment,
b)  its varying needs,
c)  its particular objectives,
d)  the products it provides,
e)  the processes it employs,
f)  its size and organizational structure.
It is not the intent of this International Standard to imply uniformity in the structure of quality man-
agement systems or uniformity of documentation.
The quality management system requirements specified in this International Standard are comple-
mentary to requirements for products. Information marked “NOTE” is for guidance in understanding
or clarifying the associated requirement.
This International Standard can be used by internal and external parties, including certification bodies,
to assess the organization’s ability to meet customer, statutory and regulatory requirements applicable
to the product, and the organization’s own requirements.
The quality management principles stated in ISO 9000 and ISO 9004 have been taken into consideration
during the development of this International Standard.
A key objective of this International Standard is to define harmonized primary packaging material
requirements. It includes some particular requirements for primary packaging materials, which are derived
from Good Manufacturing Practices for the production, control, etc. of medicinal products.
vi © ISO 2015 – All rights reserved

ISO 15378:2015(E)
Process approach
ISO 9001:2008, Quality management systems — Requirements
0.2  Process approach
This International Standard promotes the adoption of a process approach when developing, implementing
and improving the effectiveness of a quality management system, to enhance customer satisfaction by
meeting customer requirements.
For an organization to function effectively, it has to determine and manage numerous linked activities.
An activity or set of activities using resources, and managed in order to enable the transformation of
inputs into outputs, can be considered a process. Often the output from one process directly forms the
input to the next.
The application of a system of processes within an organization, together with the identification and
interactions of these processes, and their management to produce the desired outcome, can be referred
to as the “process approach”.
An advantage of the process approach is the ongoing control that it provides over the linkage between the
individual processes within the system of processes, as well as over their combination and interaction.
When used within a quality management system, such an approach emphasizes the importance of
a)  understanding and meeting requirements,
b)  the need to consider processes in terms of added value,
c)  obtaining results of process performance and effectiveness, and
d)  continual improvement of processes based on objective measurement.
The model of a process-based quality management system shown in Figure 1 illustrates the process
linkages presented in Clauses 4 to 8. This illustration shows that customers play a significant role in
defining requirements as inputs. Monitoring of customer satisfaction requires the evaluation of informa-
tion relating to customer perception as to whether the organization has met the customer requirements.
The model shown in Figure 1 covers all the requirements of this International Standard, but does not
show processes at a detailed level.
NOTE  In addition, the methodology known as “Plan-Do-Check-Act” (PDCA) can be applied to all pro-
cesses. PDCA can be briefly described as follows.
Plan:  establish the objectives and processes necessary to deliver results in accordance with customer
requirements and the organization’s policies.
Do:  implement the processes.
Check:  monitor and measure processes and product against policies, objectives and requirements for
the product and report the results.
Act:  take actions to continually improve process performance
ISO 15378:2015(E)
Continual improvement of
the quality management system
Management
responsibility
Customers
Customers
Measurement,
Resource
Satisfaction
analysis and
management
improvement
Input
Output
Product
Requirements Product
realization
Key
value-adding activities
information flow
Figure 1 — Model of a process-based quality management system
Relationship with ISO 9004
ISO 9001:2008, Quality management systems — Requirements
0.3  Relationship with ISO 9004
ISO 9001 and ISO 9004 are quality management system standards which have been designed to com-
plement each other, but can also be used independently.
ISO 9001 specifies requirements for a quality management system that can be used for internal appli-
cation by organizations, or for certification, or for contractual purposes. It focuses on the effectiveness
of the quality management system in meeting customer requirements.
At the time of publication of this International Standard, ISO 9004 is under revision. The revised edition
of ISO 9004 will provide guidance to management for achieving sustained success for any organization
in a complex, demanding, and ever changing, environment. ISO 9004 provides a wider focus on quality
management than ISO 9001; it addresses the needs and expectations of all interested parties and their
satisfaction, by the systematic and continual improvement of the organization’s performance. However,
it is not intended for certification, regulatory or contractual use.
viii © ISO 2015 – All rights reserved

ISO 15378:2015(E)
Compatibility with other management systems
This International Standard incorporates the requirements of ISO 9001:2008 and, additionally, particular
requirements for primary packaging materials, which are derived and adapted, as appropriate, from Good
Manufacturing Practices for the production and control of medicinal products.
ISO 9001:2008, Quality management systems — Requirements
0.4  Compatibility with other management systems
During the development of this International Standard, due consideration was given to the provisions of
ISO 14001:2004 to enhance the compatibility of the two standards for the benefit of the user community.
Annex A shows the correspondence between ISO 9001:2008 and ISO 14001:2004.
This International Standard does not include requirements specific to other management systems, such
as those particular to environmental management, occupational health and safety management, financial
management or risk management. However, this International Standard enables an organization to align
or integrate its own quality management system with related management system requirements. It is
possible for an organization to adapt its existing management system(s) in order to establish a quality
management system that complies with the requirements of this International Standard.
NOTE ISO 9001:2008, Annex A is not included in this International Standard.
INTERNATIONAL STANDARD ISO 15378:2015(E)
Primary packaging materials for medicinal products —
Particular requirements for the application of ISO
9001:2008, with reference to Good Manufacturing
Practice (GMP)
1 Scope
1.1 General
This International Standard specifies requirements for a quality management system where an organization
needs to demonstrate its ability to provide primary packaging materials for medicinal products, which
consistently meet customer requirements, including regulatory requirements and International Standards
applicable to primary packaging materials.
In this International Standard, the term “if appropriate” is used several times. When a requirement
is qualified by this phrase, it is deemed to be “appropriate” unless the organization can document a
justification otherwise.
ISO 9001:2008, Quality management systems — Requirements
1.1  General
This International Standard specifies requirements for a quality management system where an organ-
ization
a)  needs to demonstrate its ability to consistently provide product that meets customer and applicable
statutory and regulatory requirements, and
b)  aims to enhance customer satisfaction through the effective application of the system, including
processes for continual improvement of the system and the assurance of conformity to customer and
applicable statutory and regulatory requirements.
NOTE 1  In this International Standard, the term “product” only applies to
a)  product intended for, or required by, a customer,
b)  any intended output resulting from the product realization processes.
NOTE 2  Statutory and regulatory requirements can be expressed as legal requirements.
ISO 15378:2015(E)
1.2 Application
This International Standard is an application standard for the design, manufacture and supply of primary
packaging materials for medicinal products. It is also applicable for certification purposes.
ISO 9001:2008, Quality management systems — Requirements
1.2  Application
All requirements of this International Standard are generic and are intended to be applicable to all
organizations, regardless of type, size and product provided.
Where any requirement(s) of this International Standard cannot be applied due to the nature of an
organization and its product, this can be considered for exclusion.
Where exclusions are made, claims of conformity to this International Standard are not acceptable
unless these exclusions are limited to requirements within Clause 7, and such exclusions do not affect
the organization’s ability, or responsibility, to provide product that meets customer and applicable stat-
utory and regulatory requirements.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 9001:2008, Quality management systems — Requirements
2  Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO 9000:2005, Quality management systems — Fundamentals and vocabulary
ISO 14698-1, Cleanrooms and associated controlled environments — Biocontamination control — Part 1:
General principles and methods
ISO 14698-2, Cleanrooms and associated controlled environments — Biocontamination control — Part 2:
Evaluation and interpretation of biocontamination data
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 9000 and the following apply.
ISO 9001:2008, Quality management systems — Requirements
3  Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 9000 apply.
Throughout the text of this International Standard, wherever the term “product” occurs, it can also
mean “service”.
Additional terms and definitions used in this International Standard are specific to Good Manufacturing
1)
Practices applicable to the manufacture of primary packaging materials for medicinal products.

1) The systematic used for the grouping of the terms and definitions in this International Standard is based on that
used in ISO 9000.
2 © ISO 2015 – All rights reserved

ISO 15378:2015(E)
3.1 Terms relating to quality
3.1.1
customer complaint
information provided by a customer about deficiencies and/or nonconformities
Note 1 to entry: The information can be verbally communicated or written.
Note 2 to entry: The subject of a complaint can include primary packaging material (3.4.18.1) quality, quantity or
supply.
3.2 Terms relating to management
3.2.1
Good Manufacturing Practice
GMP
quality control (3.2.2) and quality assurance applied in manufacturing (3.4.15)
Note 1 to entry: to entry: For the definitions of quality control (3.2.2) and quality assurance, see ISO 9000:2005,
3.2.10 and 3.2.11.
Note 2 to entry: Requirements for Good Manufacturing Practice in the pharmaceutical industry are specified in a
quality assurance standard. See Reference [32].
Note 3 to entry: Good Manufacturing Practice (GMP) for primary packaging material (3.4.18.1) requires, in
addition to suitable provision of personnel, premises and equipment, a quality management system that includes
controls for incoming starting materials (3.4.28), manufacture, corresponding documentation, factory hygiene,
final inspection (3.8.5), records of distribution, processing of complaints and self-inspection.
Note 4 to entry: GMP and current Good Manufacturing Practice (cGMP) are equivalent. GMP guidelines are
continually updated to the ever-changing requirements of the state-of-the-art. This has resulted in the term cGMP
sometimes being used. The pharmaceutical industry expects that organizations (3.3.1) take account of current GMP
within their continual improvement programmes.
3.2.2
quality control
part of quality management focused on fulfilling quality requirements
Note 1 to entry: Quality control includes checking or testing that specifications (3.7.3) are met.
[SOURCE: ISO 9000:2005, 3.2.10]
3.3 Terms relating to organization
3.3.1
organization
group of people and facilities with an arrangement of responsibilities, authorities and relationships
Note 1 to entry: In this International Standard, the organization is the company manufacturing (3.4.15) the
primary packaging material (3.4.18.1).
[SOURCE: ISO 9000:2005, 3.3.1 modified by adding note 1 to entry]
3.3.2
outsourcing
provision of all or part of a process by another organization (3.3.1)
Note 1 to entry: Outsourcing is often referred to as subcontracting.
ISO 15378:2015(E)
3.3.3
quality unit
organizational unit which fulfils both quality assurance (QA) and quality control (QC) (3.2.2) responsibilities
Note 1 to entry: The quality unit(s) can consist of separate QA and QC units or of a single individual (or group),
depending upon the size and structure of the organization (3.3.1).
3.4 Terms relating to processes and product
3.4.1
air-lock
enclosed space to control air-flow
Note 1 to entry: The space typically has at least two interlocked doors between two or more rooms, used either by
people or for goods, to control for different conditions, e.g. cleanliness, air-flow upon entering.
3.4.2
assembly
fitting together of primary packaging materials (3.4.18.1) and/or components
Note 1 to entry: Examples can include pipette assemblies for filling, prepared components of injection systems or
positioning of needle shields on prefillable syringes.
3.4.3
cleanroom
room in which the concentration of airborne particles is controlled, and which is constructed and used in a
manner to minimize the introduction, generation, and retention of particles inside the room, and in which
other relevant parameters, e.g. temperature, humidity and pressure are controlled as necessary
[SOURCE: ISO 14644-1:1999, 2.1.1]
3.4.4
clean zone
dedicated space in which the concentration of airborne particles is controlled, and which is constructed and
used in a manner to minimize the introduction, generation and retention of particles inside the zone, and in
which other relevant parameters, e.g. temperature, humidity and pressure, are controlled as necessary
Note 1 to entry: This zone may be open or enclosed and may or may not be located within a cleanroom (3.4.3).
[SOURCE: ISO 14644-1:1999, 2.1.2]
3.4.5
contamination
introduction of any unwanted material into the primary packaging material (3.4.18.1)
Note 1 to entry: A finished product (3.4.11) can be contaminated by physical (particulate), chemical or biological
(bio- and endotoxin burden) action.
Note 2 to entry: Contamination can oc
...