SIST EN ISO 15378:2007

SLOVENSKI STANDARD
SIST EN ISO 15378:2007
01-november-2007
Primarni embalažni materiali za medicinske proizvode - Posebne zahteve za
uporabo ISO 9001:2000 v povezavi z dobro proizvodno prakso (DPP) (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)
(ISO 15378:2006)
Primärverpackungen für Arzneimittel - Besondere Anforderungen für die Anwendung von
ISO 9001:2000 entsprechend der Guten Herstellungspraxis (GMP) (ISO 15378:2006)
Matériaux d'emballage primaire pour médicaments - Exigences particulieres pour
l'application de l'ISO 9001:2000 prenant en considération les Bonnes Pratiques de
Fabrication (BPF) (ISO 15378:2006)
Ta slovenski standard je istoveten z: EN ISO 15378:2007
ICS:
03.120.10 Vodenje in zagotavljanje Quality management and
kakovosti quality assurance
11.040.01 Medicinska oprema na Medical equipment in general
splošno
SIST EN ISO 15378:2007 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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EUROPEAN STANDARD
EN ISO 15378
NORME EUROPÉENNE
EUROPÄISCHE NORM
July 2007
ICS 11.040.01; 03.120.10

English Version
Primary packaging materials for medicinal products - Particular
requirements for the application of ISO 9001:2000, with
reference to Good Manufacturing Practice (GMP) (ISO
15378:2006)
Matériaux d'emballage primaire pour médicaments - Primärverpackungen für Arzneimittel - Besondere
Exigences particulières pour l'application de l'ISO Anforderungen für die Anwendung von ISO 9001:2000
9001:2000 prenant en considération les Bonnes Pratiques entsprechend der Guten Herstellungspraxis (GMP) (ISO
de Fabrication (BPF) (ISO 15378:2006) 15378:2006)
This European Standard was approved by CEN on 22 June 2007.
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 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 Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2007 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 15378:2007: E
worldwide for CEN national Members.

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EN ISO 15378:2007 (E)






Foreword



The text of ISO15378:2006 has been prepared by Technical Committee ISO/TC 76
"Transfusion, infusion and injection equipment for medical and pharmaceutical use” of the
International Organization for Standardization (ISO) and has been taken over as EN ISO
15378:2007 by Technical Committee CEN/SS F20 "Quality assurance", the secretariat of which
is held by CMC.

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 January 2008, and conflicting national
standards shall be withdrawn at the latest by January 2008.

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, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United
Kingdom.


Endorsement notice

The text of ISO 15378:2006 has been approved by CEN as EN ISO 15378:2007 without any
modifications.

2

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INTERNATIONAL ISO
STANDARD 15378
First edition
2006-03-01


Primary packaging materials for
medicinal products — Particular
requirements for the application of
ISO 9001:2000, with reference to
Good Manufacturing Practice (GMP)
Matériaux d'emballage primaire pour médicaments — Exigences
particulières pour l'application de l'ISO 9001:2000 prenant en
considération les Bonnes Pratiques de Fabrication (BPF)




Reference number
ISO 15378:2006(E)
©
ISO 2006

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ISO 15378:2006(E)
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©  ISO 2006
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
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Published in Switzerland

ii © ISO 2006 – All rights reserved

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ISO 15378:2006(E)
Contents Page
Foreword. iv
0 Introduction . v
0.1 General. v
0.2 Process approach. vi
0.3 Relationship with ISO 9004. vii
0.4 Compatibility with other management systems . viii
1 Scope . 1
1.1 General. 1
1.2 Application . 1
2 Normative references . 2
3 Terms and definitions. 2
4 Quality management system . 11
4.1 General requirements. 11
4.2 Documentation requirements. 12
5 Management responsibility . 14
5.1 Management commitment . 14
5.2 Customer focus. 14
5.3 Quality policy . 15
5.4 Planning. 15
5.5 Responsibility, authority and communication. 15
5.6 Management review. 16
6 Resource management . 17
6.1 Provision of resources. 17
6.2 Human resources. 18
6.3 Infrastructure. 19
6.4 Work environment . 19
6.5 Maintenance activities. 20
7 Product realization. 20
7.1 Planning of product realization . 20
7.2 Customer-related processes . 21
7.3 Design and development . 22
7.4 Purchasing . 25
7.5 Production and service provision. 26
7.6 Control of monitoring and measuring devices. 30
8 Measurement, analysis and improvement . 31
8.1 General. 31
8.2 Monitoring and measurement . 31
8.3 Control of nonconforming product. 33
8.4 Analysis of data . 34
8.5 Improvement . 34
Annex A (normative) GMP requirements for printed primary packaging materials. 36
Annex B (informative) Guidance on verification and validation requirements for primary
packaging materials . 40
Annex C (informative) Guidance on risk management for primary packaging materials. 49
Bibliography . 56
Index. 58

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ISO 15378:2006(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 15378 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment
for medical and pharmaceutical use.

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ISO 15378:2006(E)
0 Introduction
0.1 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 should 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
requirements text of ISO 9001:2000.
The conventions for the layout of this International Standard are the following.
⎯ Those clauses or subclauses that are quoted directly and unchanged from ISO 9001:2000 are in boxed
text.
⎯ Texts in italics contain additionally relevant GMP requirements for primary packaging materials.
⎯ GMP terms and definitions are included in Clause 3. If listed, the source is referred to in brackets.
ISO 9001:2000, Quality management systems — Requirements
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.
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ISO 15378:2006(E)
0.2 Process approach
ISO 9001:2000, Quality management systems — Requirements

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ISO 15378:2006(E)
0.3 Relationship with ISO 9004
ISO 9001:2000, Quality management systems — Requirements

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ISO 15378:2006(E)
0.4 Compatibility with other management systems
This International Standard incorporates the requirements of ISO 9001:2000 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 9001:2000, Quality management systems — Requirements


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INTERNATIONAL STANDARD ISO 15378:2006(E)

Primary packaging materials for medicinal products —
Particular requirements for the application of ISO 9001:2000,
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 9001:2000, Quality management systems — Requirements
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 9001:2000, Quality management systems — Requirements

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ISO 15378:2006(E)
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 9001:2000, Quality management systems — Requirements
ISO 9001:2000, Quality management systems — Requirements
ISO 14644-1:1999, Cleanrooms and associated controlled environments — Part 1: Classification of air
cleanliness
ISO 14644-2:2000, Cleanrooms and associated controlled environments — Part 2: Specifications for testing
and monitoring to prove continued compliance with ISO 14644-1
ISO 14644-3, Cleanrooms and associated controlled environments — Part 3: Test methods
ISO 14644-4:2001, Cleanrooms and associated controlled environments — Part 4: Design, construction and
start-up
ISO 14644-5, Cleanrooms and associated controlled environments — Part 5: Operations
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 9000 and the following apply.
ISO 9001:2000, Quality management systems — Requirements
NOTE 1 In addition, the terminology subcontractor (see 3.61) and outsourcing (see 3.34) is used for this International
Standard.
NOTE 2 The term “subcontractor” is still predominantly used in the pharmaceutical packaging industry over that of
“supplier”.
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ISO 15378:2006(E)
Additional terms and definitions used in this International Standard are specific to Good Manufacturing
Practices applicable to the manufacture of primary packaging materials for medicinal products.
3.1
air-lock
enclosed space to control air-flow
NOTE The space typically has at least two interlocked doors between two or more rooms, used by either people or
for goods, to control for different conditions, e.g. cleanliness, air-flow upon entering.
3.2
approved
confirmed conformity status
NOTE Conformity can be confirmed for any stage of the process (starting materials, process aids, packaging material
or finished product).
3.3
assembly
fitting together of primary packaging materials (3.35.1) and/or components
NOTE Examples may include pipette assemblies for filling, prepared components of injection systems or positioning
of needle shields on prefillable syringes.
3.4
automated inspection
conformity evaluation performed by inspection equipment without manual intervention
NOTE The inspection equipment can include optoelectronics (cameras), laser systems, ultrasonics and their
associated data processing functions or others.
3.5
batch
lot
defined quantity of primary packaging material (3.35.1) manufactured in one process or series of processes
intended to have uniform characteristics with consistent, homogeneous quality
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.
NOTE 2 In the case of continuous production, the batch is a fraction of the production defined either as a fixed quantity
or as the amount produced in a fixed time interval.
3.6
batch document
batch record
documents and records that provide a history of the batch (3.5), including information relating to its production
and control, and which facilitate its traceability (3.63)
3.7
batch number
lot number
unique identifier to identify a batch or lot (3.5)
NOTE A batch number can be a combination of numbers, letters and/or symbols which identifies a batch (or lot) and
from which the production and distribution history can be determined.
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ISO 15378:2006(E)
3.8
batch release
decision to release the batch (3.5) for sale or supply, following a formal review of the batch document (3.6)
performed by the quality unit (3.41) or a person authorized by the quality unit(s)
3.9
calibration
process of checking or adjusting (by comparison with a reference standard) the accuracy of a measuring
instrument
NOTE Calibration can also be described as the set of operations which establish, under specified conditions, the
relationship between values indicated by a measuring instrument or values represented by a material measure, and the
corresponding known values of a reference standard.
3.10
change control
documented control of changes
NOTE Changes may include, e.g. changes in raw materials, specifications, facilities, equipment, production
processes and test methods.
3.11
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
[ISO 14644-1:1999, 2.1.1]
3.12
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
[ISO 14644-1:1999, 2.1.2]
NOTE This zone may be open or enclosed and may or may not be located within a clean room.
3.13
contamination
introduction of any unwanted material into the primary packaging material (3.35.1)
NOTE 1 A finished product can be contaminated by physical (particulate), chemical or biological (bio- and endotoxin
burden) action.
NOTE 2 Contamination can occur during production, packaging, storage and/or distribution from contaminated air
systems, personnel, sampling equipment, materials, premises or containers.
3.14
controlled area
controlled environment
area or environment constructed and operated to control the possible introduction of potential contaminants
NOTE 1 The area is typically constructed and operated to control the introduction of potential contamination and the
consequences of accidental release of living organisms.
NOTE 2 An appropriate pressure differential allows for the efficient removal of airborne contaminants, potential
contamination and the consequences of accidental release.
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ISO 15378:2006(E)
3.15
cross-contamination
mix-up
contamination (3.13) of a material or of a product with another material or product
[EC Guide to GMP]
NOTE Cross-contamination may also be referred to as admixture.
3.16
customer complaint
customer information about deficiencies and/or nonconformities
NOTE 1 The information may be verbally communicated or written.
NOTE 2 The subject of a complaint can include primary packaging material quality, quantity or supply.
3.17
date of manufacture
date on which one of the first stages in the process of manufacture of the primary packaging material, or the
packaging, or the final release, occurs, and which may be subject to customer agreement
3.18
deviation
departure from an approved standard operating procedure (SOP) (3.58) or established standard
3.19
documented procedure
procedure that is established, documented, authorized, implemented and maintained
3.20
double-check
documented verification (3.65) of an activity, result or record by a second person or system
NOTE A second in-process control check signature, production and quality records for a batch signed by a second
person or electronic checks can be part of this verification process. Double-checks typically are signed by a second
person.
3.21
expiration date
expected suitable use limit. See also definition shelf-life (3.56)
NOTE This is typically the period during which a primary packaging material is expected to remain suitable for use if
stored under defined conditions and after which it should not be used.
3.22
final inspection
tests carried out on the finished product (3.23) to determine compliance with the specification
3.23
finished product
primary packaging material (3.35.1) which has completed all stages of production (3.37)
3.24
Good Manufacturing Practice
GMP
quality control and quality assurance applied in manufacturing (3.29)
NOTE 1 For the definitions of quality control and quality assurance see ISO 9000:2000 (3.2.10 and 3.2.11).
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ISO 15378:2006(E)
NOTE 2 Requirements for Good Manufacturing Practice in the pharmaceutical industry are specified in a quality
assurance standard entitled “EC Guide to Good Manufacturing Practice”.
NOTE 3 Good Manufacturing Practice (GMP) for primary packaging materials requires, in addition to suitable provision
of personnel, premises and equipment, a quality management system that includes controls for incoming starting materials,
manufacture, corresponding documentation, factory hygiene, final inspection, records of distribution, processing of
complaints and self-inspection.
NOTE 4 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 resulted in the term cGMP sometimes being used.
The pharmaceutical industry expects that organizations take account of current GMP within their continual improvement
programmes.
3.25
homogeneity
uniformity of characteristics and their values throughout a defined quantity of material
NOTE Homogeneity can include uniformity of materials or certain characteristics of materials of special significance.
3.26
in-process control
actions taken during the production process to test product conformity to its specification
NOTE 1 Monitoring processes and adjusting the means of production can be necessary to meet product requirements.
NOTE 2 The control of the environment or equipment can also be regarded as a part of in-process control.
3.27
intermediate product
primary packaging material (3.35.1) which has completed some but not all production stages
NOTE An intermediate product needs further processing before it becomes a finished product.
3.28
line clearance
removal (line purge) of everything associated with the prior production run
NOTE Line clearance typically is done previous to a production run to prevent any error and cross-contamination.
Typically it is required that a production facility (line) and its associated working area are completely clear of all materials,
waste, products, samples, documents etc. used in the prior production run before the introduction of materials, product
samples, documents etc. needed for the commencement of the next production run.
3.29
manufacturing
all operations of purchase of materials and primary packaging materials (3.35.1), production (3.37),
quality control (3.39), release, sto
...