ISO
13926-2
INTERNATIONAL
STANDARD
Third edition
2017-11
Pen systems —
Plunger stoppers for pen-injectors for
Pmaerdt 2ic:a l use
Systèmes de stylos-injecteurs —
Partie 2: Bouchons-pistons pour stylos-injecteurs à usage médical
Reference number
ISO 13926-2:2017(E)
Copyright International Organization for Standardization
Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly
No reproduction or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT ©
ISO 2017
--,,,,`,,,,,`,`,`,,,,,```,`-`-`,,`,,`,`,,`--- ISO 13926-2:2017(E) COPYRIGHT PROTECTED DOCUMENT © ISO 2017, 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 --,,,,,,,,,,,,,,,,,`-`-`,,`,,`,`,,`--- Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reprodu i ct i ion or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT © ISO 2017 – All rights reserved ISO 13926-2:2017(E) Contents Page Foreword iv Introduction v ........................................................................................................................................................................................................................................ 1 Scope 1 .................................................................................................................................................................................................................................. 2 Normative references 1 ................................................................................................................................................................................................................................. 3 Terms and definitions 1 ...................................................................................................................................................................................... 4 Classification 1 ..................................................................................................................................................................................... 5 Shape and dimensions 2 ............................................................................................................................................................................................................ 6 Designation 3 .................................................................................................................................................................................... 7 Material 3 ................................................................................................................................................................................................................ 8 Requirements 3 .......................................................................................................................................................................................................................... .......................................................................................................................................................................................................... 8.1 General ...........................................................................................................................................................................................................3 8.2 Physical requirements ......................................................................................................................................................................3 8.2.1 Hardness .................................................................................................................................................................................3 8.2.2 Freedom from leakage ................................................................................................................................................3 8.2.3 Initiating and sustaining forces ...........................................................................................................................4 8.2.4 Resistance to ageing ......................................................................................................................................................4 8.3 Chemical requirements....................................................................................................................................................................4 9 Labelling 4 8.4 Biological requirements ..................................................................................................................................................................4 Annex A Leakage test 5 ........................................................................................................................................................................................................................ Bibliography 7 (normative) .......................................................................................................................................................................... ................................................................................................................................................................................................................................ Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT iii --``,,,,`,,,,,`,`,`,,,,,,--,,,,,,,--- ISO 13926-2:2017(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 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 the following URL: www.iso.org/iso/foreword.html. Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use This document was prepared by Technical Committee ISO/TC 76, . This third edition cancels and replaces the second edition (ISO 13926-2:2011), which has been technically revised. It also incorporates the Amendment ISO 13926-2:2011/Amd. 1:2015. The main changes codmpdared to dthe previous edition are as follows: d — the dimensions 1, 2 and 3 in Table 1 have been changed from normative to informative; 2 is required to align with ISO 13926-1; — Formula (A.1) has been corrected. A list of all parts in the ISO 13926 series can be found on the ISO website. --``,,,,,,,,,,,,,,,,```,--,,,,,,,---
Copyright International Organization for Standardization
Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly
No reprodu i ct v ion or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT © ISO 2017 – All rights reserved
ISO 13926-2:2017(E)
Introduction
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.
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.
--,,,,`,,,,,`,`,`,,,,,```,`-`-`,,`,,`,`,,`--- Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT v --,,,,,,,,,,,,,,,,,`-`-`,,`,,`,`,,`--- Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT INTERNATIONAL STANDARD ISO 13926-2:2017(E) Pen systems — Plunger stoppers for pen-injectors for medical use Part 2: 1 Scope This document specifies the material, performance requirements and labelling and gives recommendations for shape and dimensions of plunger stoppers for pen-injectors for medical use. NOTE The potency, purity, stability and safety of a medicinal product during its manufacture and storage can strongly be 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 refeRruebnbceers —, th Teo llaetreasntc eeds iftoior np roofd tuhcet sr e—fe rPeanrcte 1d: Ddoimcuenmseionnt a(li ntoclleurdainncge asny amendments) applies. ISO 3302-1, Rubber, vulcanized or thermoplastic — Determination of indentation hardness — Part 1: Durometer method (Shore hardness) ISO 7619-1, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 1: Extractables in aqueous autoclavates ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 4: Biological requirements and test methods ISO 8871-4, Needle-based injection systems for medical use — Requirements and test methods — Part 3: Finished containers ISO 11608-3, Pen systems — Part 1: Glass cylinders for pen-injectors for medical use ISO 13926-1, Pen systems — Part 3: Seals for pen-injectors for medical use ISO 13926-3, 3 Terms and definitions No terms and definitions are listed in this document. ISO and IEC maintain terminological databases for use in standardization at the following addresses: — IEC Electropedia: available at http://www.electropedia.org/ — ISO Online browsing platform: available at http://www.iso.org/obp 4 Classification Plunger stoppers shall be classified as follows: — Type A1: plunger stoppers with ribs; — Type A2: plunger stoppers without ribs; Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT ---`,,`,`,,`,,`-`-`,,,,,,,,,,,,,,,,,``--
ISO 13926-2:2017(E)
— Type A3: plunger stoppers with ribs and dome.
5 Shape and dimensions
5.1
The shapeds and dimensions of plunger stoppers as shown in Figure 1 are as given in Table 1.
The dimension 1 shall be specified by using the selected cartridges according to ISO 13926-1 and the
selected seal as per ISO 13926-3. The system can then be validdatded ads described in ISO 11608-3.
The dimensions that refer to the plunger stopper diameters ( 1, 2, 3) are informative.
Dimensions in millimetres
a) Type A1 b) Type A2 c) Type A3
Key
d d d
h
1, 2, 3 diameters of plunger stoppers
height of plunger stoppers
a
The height shall be agreed between the manufacturer and the user.
[Figure 1 — Shape and dimensions of plunger stoppers for pen-injectors for medical use]
Table 1 — Typical examples for dimensions of plunger stoppers for pen-injectors for medical use
Diameter
Dimensions in millimetres
Nominal inner diameter
d d d
of the glass cylinder
a 1 3 2
min. min. max.
6,85 7,1 7,0 6,6
8,65 8,9 8,8 8,4
9,25 9,5 9,4 9,0
9,65 9,9 9,8 9,4
a
Values in accordance with ISO 13926-1.
The height shall be agreed between the manufacturer and the user.
Corresponding glass barrels are recommended in ISO 13926-1 and the corresponding seals in
ISO 13926-3.
Copyright International Organization for Standardization
Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly
No reproduction or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT © ISO 2017 – All rights reserved
--`,,,,,,,,,,,,,,,,```,--,,,,,,,---
ISO 13926-2:2017(E)
The compatibility of the components glass barrel and rubber plunger and seals shall be thoroughly
validated as described in ISO 11608-3.
5.2
In order to avoid adhesion of the plunger stoppers to each other, there shall be spacers. The height
of the spacers shall not exceed 0,3 mm.
The shape of the spacers should be agreed between the manufacturer and the cartridge assembler.
5.3
If not otherwise specified, general dimensional tolerances shall be in accordance with ISO 3302-1.
6 Designation
Plunger stoppers can be designated adccording to their type (see Clause 4 and Figure 1). The designation
shall be expressed as the word "plunger", followed by a reference to this document, followed by the
inner diameter of the glass cylinder, 2, followed by the type letter.
EXAMPLE Designation of a plunger stopper Type A1 complying with the requirements of this document for a
glass cylinder with an inner diameter Pofl u6n,8g5e mr mIS:O 13926-2 – 6,85 – A1
7 Material
Plunger stoppers shall be made from the elastomeric formulation originally tested and approved by the
end-user. The manufacturer of the plunger stoppers shall ensure the conformance of each delivery with
the type sample and the compliance with previously agreed functional and compendial requirements.
The elastomeric material shall withstand two sterilization cycles when autoclaving in saturated steam
at (121 ± 2) °C for 30 min without impairment of its function under the conditions of normal use. In case
of other sterilization methods, e.g. irradiation, the suitability of the material has to be evaluated.
8 Requirements
The requirements specified in 8.2 to 8.4 represent minimum requirements which refer to the condition of the elastomeric plunger stoppers on receipt by the user.
The hardness agreed between the manufacturer and the user shall not differ from the nominal value by more than ±5 Shore A when tested in accordance with ISO 7619-1 on special test specimen. Alternatively, the hardness can be tested on the plunger stoppers according to ISO 48. If tested according to ISO 48, the microhardness shall not differ by more than ±5 IRHD from the type sample. The manufacturer should provide suitable test specimen upon requests.
The cartridges shall be free from leakage at the plunger when tested in accordance with the method
given in Annex A.
--`,,,,,,,,,,,,,,,,```,--,,,,,,,---
Copyright International Organization for Standardization
Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly
No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT
ISO 13926-2:2017(E)
The initiating and sustaining forces are influenced by all components of the container closure systems and process parameters, e.g. siliconization. The testing of complete systems is described in ISO 11608-3. The results depend on the configuration and the pre-treatment (dry, kind of liquid, storage time, etc.).
The maximum time between the date of manufacture and the pharmaceutical use should be agreed upon between the manufacturer of the plunger stoppers and the user. The plunger stoppers shall maintain their performance characteristics throughout the entire shelf life of the medicinal product which is tested as part of the stability test by the user. NOTE Ageing depends upon the storage and handling conditions. A guide to storage of vulcanized rubber is given in ISO 2230.
The requirements in ISO 8871-1 shall apply.
The requirements in ISO 8871-4 shall apply.
9 Labelling
Packed plunger stoppers which meet the requirements of this document can be marked with the
designation given in Clause 6.
Copyright International Organization for Standardization
Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly
No reproduction or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT © ISO 2017 – All rights reserved
---,,,,,,,--,```,,,,,,,,,,,,,,,,``-- ISO 13926-2:2017(E) Annex A L(enaokrmagaet itvees)t A.1 Principle Water-filled cartridges are prepared using the plunger stoppers to be tested. By means of a suitable device, a force is applied to the plunger stopper during a defined time interval. Any observed leakage is recorded. The leakage test of the plunger stoppers and the seals (see ISO 13926-3) can be combined. A.2 Apparatus A.2.1 Cartridge cylinders , with a silicone-treated inner surface in accordance with ISO 13926-1. A.2.2 Seals , in accordance with ISO 13926-3. A.2.3 Plungers , in accordance with this document. A.2.4 Suitable equipment , to prepare water-filled cartridges. A.2.5 Cartridge holder , for example, as specified in ISO 11608-3. A.2.6 Device , capable to apply a force as calculated in accordance with A.3.2. A.3 Procedure A.3.1 Take 10 cartridges and fill them with water practically air-free using the plunger stoppers to be tested. The water may be replaced by a coloured solution in order to improve the visibility of the leakage. A.3.2 F Place the first cartridge, mounted in the cartridge holder (A.2.5), into the pressurizing device (A.2.6), and appNly a f(or2ce), , as calculated in accordance with Formula A.1, for 1 min. F =0,64 × d mm (A.1) wherFe d is the force to be applied in newton (N); d is the inner diameter of the glass cylinder in millimetres (mm) in accordance with ISO 13926-1 (in ISO 13926-1, the inner diameter of the glass cylinder is designated ); 0,64 is a correction factor in newton/square millimetres (N/mm ). Check for leakage at the plunger stopper. Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT --``,,,,,,,,,,,,,,,,```,--,,,,,,,---
ISO 13926-2:2017(E)
SAFETY PRECAUTIONS — Adequate safety measures should be in place to protect the operator.
A.3.3
Repeat the operation described in A.3.2 on the remaining cartridges.
A.4 Expression of results
Report the number of leakages observed at the plunger stoppers.
Report if the testing of the plunger stoppers and the seals (see ISO 13926-3) has been combined.
--,,,,`,,,,,`,`,`,,,,,```,`-`-`,,`,,`,`,,`--- Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or networking permitted without license from IHS Not for Resale, 10/14/2019 19:22:29 MDT © ISO 2017 – All rights reserved ISO 13926-2:2017(E) Bibliography Rubber, vulcanized or thermoplastic — Determination of hardness (hardness between 10 IRHD and 100 IRHD) [1] ISO 48, Rubber products — Guidelines for storage [2] ISO 2230, Primary packaging materials for medicinal products — Particular requirements for the application of ISO 9001:2015, with reference to good manufacturing practice (GMP) [3] ISO 15378, [4] EC Guide to Good Manufacturing Practice for Medicinal Products, III/2244/87, rev. 3 — January 1998 as amended --,,,,,,,,,,,,,,,,,`-`-`,,`,,`,`,,`--- 7 Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reproduction or network©ing pIeSrmOit te2d0 w1ith7ou t– lic Aenlsle rfroimg hIHtSs reserved Not for Resale, 10/14/2019 19:22:29 MDT ISO 13926-2:2017(E) ICS 11.040.25 Price based on 7 pages Copyright International Organization for Standardization Provided by IHS Markit under license with ANSI Licensee=Becton Dickinson - Loc 1 - 61, 64/5984713001, User=Chiu, Shelly No reprodu©ctio nI oSr One t2wo0rk1ing7 p e–rm Aittelld wriithgohutt lisce rnsees freomr vIHeSd Not for Resale, 10/14/2019 19:22:29 MDT --``,,,,`,,,,,`,`,`,,,,,,--,,,,,,,`---
Applying these regulatory guidelines in practice? Use our free validated calculators for risk management, sampling, and environmental monitoring.