ISO 8536-6:2025
(Main)Infusion equipment for medical use — Part 6: Freeze drying closures for infusion bottles
Infusion equipment for medical use — Part 6: Freeze drying closures for infusion bottles
This document specifies the shape, dimensions, material, performance requirements and labelling for the type of closure for infusion bottles, as described in ISO 8536-1, that is used in connection with the freeze-drying (or lyophilization) of drugs and biological materials. The dimensional requirements are not applicable to barrier-coated closures. Closures specified in this document are intended for single use only. NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can be strongly affected by the nature and performance of the primary packaging.
Matériel de perfusion à usage médical — Partie 6: Bouchons à lyophilisation pour flacons de perfusion
General Information
Relations
Standards Content (Sample)
International
Standard
ISO 8536-6
Fourth edition
Infusion equipment for medical use —
2025-03
Part 6:
Freeze drying closures for
infusion bottles
Matériel de perfusion à usage médical —
Partie 6: Bouchons à lyophilisation pour flacons de perfusion
Reference number
© ISO 2025
All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Shape and dimensions . 2
5 Designation . 3
6 Material. 3
7 Requirements . 4
7.1 General .4
7.2 Physical requirements .4
7.2.1 Hardness .4
7.2.2 Fragmentation (coring) .4
7.2.3 Spike penetration force .4
7.2.4 Spike retention/sealability .4
7.2.5 Resistance to ageing .4
7.2.6 Residual moisture .5
7.3 Chemical requirements . .5
7.4 Biological requirements .5
8 Labelling . 5
Annex A (normative) Determination of fragments . 6
Annex B (normative) Determination of spike penetration force . 8
Annex C (normative) Spike retention/sealability . 10
Annex D (normative) Closure piercing device .12
Annex E (informative) Determination of residual moisture .13
Bibliography .16
iii
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 document should be noted. This document was drafted in accordance with the editorial rules of the
ISO/IEC Directives, Part 2 (see http://www.iso.org/directives).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
http://www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement. For an explanation of the voluntary nature of standards, the meaning of ISO
specific terms and expressions related to conformity assessment, as well as information about ISO's
adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
http://www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and
blood processing equipment for medical and pharmaceutical use.
This fourth edition cancels and replaces the third edition (ISO 8536-6:2016), which has been technically
revised.
The main changes are as follows:
[1]
— reference to has been removed:
— reference to ISO 8536-7 has been added;
— information regarding fragment size and sterilization step have been clarified.
A list of all parts in the ISO 8536 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
iv
Introduction
Freeze drying closures are put on the top of infusion bottles after filling, leaving sufficient openings for the
sublimation process and vacuum. At the end of the drying process, they can be fully inserted into the glass
container by hydraulic or mechanical means in the vacuum chamber.
Freeze drying closures can pick up water during shipping, storage, washing and steam sterilization cycles,
which is difficult to remove in a subsequent drying cycle. As a consequence, the freeze drying closures are
usually loaded with residual moisture. Depending upon the mass of the freeze-dried product and the degree
of its sensitivity to water, the residual moisture in the rubber material can spoil the freeze-dried preparation
during storage.
These specific process requirements have been addressed in this document by specifying relevant
requirements for freeze drying closures including a test method on determination of residual moisture.
Primary packaging components made of elastomeric materials are an integral part of medicinal products
and thus the principles of current Good Manufacturing Practices (cGMP) apply to the manufacturing of these
components.
[2]
Principles of cGMP are described in, for example, ISO 15378 or GMP Guidelines as published by the
European Community and the United States of America.
v
International Standard ISO 8536-6:2025(en)
Infusion equipment for medical use —
Part 6:
Freeze drying closures for infusion bottles
1 Scope
This document specifies the shape, dimensions, material, performance requirements and labelling for the
type of closure for infusion bottles, as described in ISO 8536-1, that is used in connection with the freeze-
drying (or lyophilization) of drugs and biological materials.
The dimensional requirements are not applicable to barrier-coated closures.
Closures specified in this document are intended for single use only.
NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can be
strongly affected by the nature and performance of the primary packaging.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes
requirements 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 48-4, Rubber, vulcanized or thermoplastic — Determination of hardness — Part 4: Indentation hardness by
durometer method (Shore hardness)
ISO 3302 (all parts), Rubber — Tolerances for products
ISO 8536-1, Infusion equipment for medical use — Part 1: Infusion glass bottles
ISO 8536-3, Infusion equipment for medical use — Part 3: Aluminium caps for infusion bottles
ISO 8536-7, Infusion equipment for medical use — Part 7: Caps made of aluminium-plastics combinations for
infusion bottles
ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 1: Extractables in
aqueous autoclavates
ISO 8871-4, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 4: Biological
requirements and test methods
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at http:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
fragmentation
formation of elastomeric particles that are generated when the disc or other elastomeric components that
forms part of the primary container closure is pierced by a needle, spike or other access device for filling or
delivery
Note 1 to entry: Coring is one mechanism to generate fragments.
[3]
[SOURCE: ISO 11608-3:2022 , 3.4, modified — changed "disc coring" to "coring".]
3.2
freeze-drying
lyophilization
drying process designed to remove solvents from both aqueous and non-aqueous systems by sublimation
and desorption
3.3
freeze drying closure
closure which enables the drying of a frozen pharmaceutical preparation in a vacuum chamber
4 Shape and dimensions
4.1 The dimensions of freeze drying closures shall be as given in Table 1. Figure 1 illustrates the general
design of a freeze drying closure.
Key
1 positioning element
2 spacers
NOTE The total height of the freeze drying closure, h , can vary and is subject to mutual agreement between
manufacturer and user.
Figure 1 — Example to illustrate a freeze drying closure design
Table 1 — Dimensions of freeze drying closures
Dimensions in millimetres
a
Nominal d d h h h
1 2 2 3 4
size ±0,3 ±0,2 ±0,3 min. min.
32 30,8 23,6 4,0 4 3,7
28 27,1 19,6 3,4 4 2,2
a The value of d is applied in that area which is defined by h .
2 3
4.2 If not otherwise specified, general dimensional tole
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.