SIST EN ISO 8871-2:2020
(Main)Elastomeric parts for parenterals and for devices for pharmaceutical use - Part 2: Identification and characterization (ISO 8871-2:2020)
Elastomeric parts for parenterals and for devices for pharmaceutical use - Part 2: Identification and characterization (ISO 8871-2:2020)
ISO 8871-2 specifies identification and characterization procedures applicable to elastomeric parts including coated stoppers used for drug containers and medical devices.The physical and chemical test procedures specified in this document permit the determination of the typical characteristics of elastomeric parts including coatings and surface treatments and can serve as a basis for agreements between manufacturer and user regarding the product consistency in subsequent supplies. Depending upon the type of elastomer and its application, an appropriate set of tests is selected.
Elastomere Teile für Parenteralia und für Geräte zur pharmazeutischen Verwendung - Identifizierung und Charakterisierung (ISO 8871-2:2020)
Dieses Dokument legt Verfahren zur Identifikation und Charakterisierung bei elastomeren Teilen einschließlich beschichteter Stopfen fest, die für Medikamentenbehälter und Medizinprodukte verwendet werden.
Die durch dieses Dokument zur Verfügung gestellten physikalischen und chemischen Prüfverfahren ermöglichen die Bestimmung der typischen Eigenschaften von elastomeren Teilen, einschließlich Beschichtungen und Oberflächenbehandlungen, und können als Grundlage für Vereinbarungen zwischen Hersteller und Anwender hinsichtlich der gleich bleibenden Eigenschaften des Produkts bei nachfolgenden Lieferungen dienen. Abhängig von der Elastomerart und ihrer Anwendung wird eine angemessene Reihe von Prüfungen ausgewählt.
Éléments en élastomère pour administration parentérale et dispositifs à usage pharmaceutique - Partie 2: dentification et caractérisation (ISO 8871-2:2020)
Le présent document spécifie des modes opératoires d'identification et de caractérisation applicables aux éléments en élastomère, notamment les bouchons revêtus, utilisés pour les articles de conditionnement des médicaments et les dispositifs médicaux.
Les modes opératoires d'essai physique et chimique présentés dans le présent document permettent de déterminer les caractéristiques types des éléments en élastomère, y compris les revêtements et les traitements de surface, et peuvent servir de base à des accords entre le fabricant et l'utilisateur en ce qui concerne la reproductibilité du produit lors des livraisons ultérieures. Un ensemble approprié d'essais est choisi en fonction du type d'élastomère et de l'application.
Deli iz elastomera za parenteralne farmacevtske oblike - 2. del: Identifikacija in opredelitev (ISO 8871-2:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 8871-2:2020
01-julij-2020
Nadomešča:
SIST EN ISO 8871-2:2005
SIST EN ISO 8871-2:2005/A1:2014
Deli iz elastomera za parenteralne farmacevtske oblike - 2. del: Identifikacija in
opredelitev (ISO 8871-2:2020)
Elastomeric parts for parenterals and for devices for pharmaceutical use - Part 2:
Identification and characterization (ISO 8871-2:2020)
Elastomere Teile für Parenteralia und für Geräte zur pharmazeutischen Verwendung -
Identifizierung und Charakterisierung (ISO 8871-2:2020)
Éléments en élastomère pour administration parentérale et dispositifs à usage
pharmaceutique - Partie 2: dentification et caractérisation (ISO 8871-2:2020)
Ta slovenski standard je istoveten z: EN ISO 8871-2:2020
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
SIST EN ISO 8871-2:2020 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 8871-2:2020
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SIST EN ISO 8871-2:2020
EN ISO 8871-2
EUROPEAN STANDARD
NORME EUROPÉENNE
June 2020
EUROPÄISCHE NORM
ICS 11.040.20 Supersedes EN ISO 8871-2:2004
English Version
Elastomeric parts for parenterals and for devices for
pharmaceutical use - Part 2: Identification and
characterization (ISO 8871-2:2020)
Éléments en élastomère pour administration Elastomere Teile für Parenteralia und für Geräte zur
parentérale et dispositifs à usage pharmaceutique - pharmazeutischen Verwendung - Teil 2:
Partie 2: dentification et caractérisation (ISO 8871- Identifizierung und Charakterisierung (ISO 8871-
2:2020) 2:2020)
This European Standard was approved by CEN on 21 April 2020.
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, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, 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: Rue de la Science 23, B-1040 Brussels
© 2020 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 8871-2:2020 E
worldwide for CEN national Members.
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SIST EN ISO 8871-2:2020
EN ISO 8871-2:2020 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 8871-2:2020
EN ISO 8871-2:2020 (E)
European foreword
This document (EN ISO 8871-2:2020) has been prepared by Technical Committee ISO/TC 76
"Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical
use" in collaboration with Technical Committee CEN/TC 205 “Non-active medical devices” the
secretariat of which is held by DIN.
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 December 2020, and conflicting national standards
shall be withdrawn at the latest by December 2020.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 8871-2:2004.
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, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 8871-2:2020 has been approved by CEN as EN ISO 8871-2:2020 without any
modification.
3
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SIST EN ISO 8871-2:2020
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SIST EN ISO 8871-2:2020
INTERNATIONAL ISO
STANDARD 8871-2
Second edition
2020-05
Elastomeric parts for parenterals and
for devices for pharmaceutical use —
Part 2:
Identification and characterization
Éléments en élastomère pour administration parentérale et dispositifs
à usage pharmaceutique —
Partie 2: Identification et caractérisation
Reference number
ISO 8871-2:2020(E)
©
ISO 2020
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
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
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Tests . 2
4.1 General . 2
4.2 Hardness . 2
4.3 Density . 2
4.4 Ash . 3
4.5 Infrared spectrum . 3
4.5.1 Material . 3
4.5.2 Coating . 3
4.6 Compression set . . 3
4.7 Swelling . 3
4.8 Development of a fingerprint by gas chromatography . 3
4.9 Detection of volatile substances by gas chromatography . 4
4.10 Determination of residual moisture . 4
4.11 Determination of fingerprint by thermogravimetric analysis (TGA) . 4
4.12 Determination of extractables in aqueous autoclavates . 4
5 Preparation of samples for testing . 4
5.1 Treatment before testing . 4
5.2 Number of samples needed for the tests . 4
6 Reagents and materials . 5
Annex A (informative) Identification of elastomeric material by pyrolysis IR .6
Annex B (informative) Determination of compression set . 8
Annex C (informative) Swelling behaviour in oils .10
Annex D (informative) Development of a fingerprint by gas chromatography .12
Annex E (informative) Analysis of volatile components by headspace gas chromatography .14
Annex F (informative) Determination of residual moisture .16
Annex G (informative) Determination of a fingerprint by thermal gravimetry (TG) .17
Annex H (informative) Determination of the elastomer identity and verification of the
presence of a coating by surface infrared spectroscopy [attenuated total reflection
(ATR)] .20
Bibliography .23
© ISO 2020 – All rights reserved iii
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(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 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
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, in collaboration with the European
Committee for Standardization (CEN) Technical Committee CEN/TC 205, Non-active medical devices, in
accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
This second edition cancels and replaces the first edition (ISO 8871-2:2003), which has been technically
revised. It also incorporates the Amendment ISO 8871-2:2003/Amd.1:2005. The main changes compared
to the previous edition are as follows:
— expansion of the scope to include coated stoppers;
— addition of terms and definitions;
— addition of H.6 on the interpretation of results for ATR.
A list of all parts in the ISO 8871 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 © ISO 2020 – All rights reserved
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
Introduction
The elastomeric parts specified in the ISO 8871 series are produced from rubber. However, rubber is not
a unique entity, since the composition of rubber materials can vary considerably. The base elastomer
and the type of vulcanization have a major influence on the principle characteristics of an individual
rubber material, as do additives such as fillers, softeners and pigments. These might have a significant
effect on the overall properties. Polymer coatings or films are often applied to either entire or partial
surface(s) of a rubber component to impart certain physical or chemical properties. The effectiveness,
purity, stability and safe handling of a drug preparation can be affected adversely during manufacture,
storage and administration if the rubber part used has not been properly selected and validated
(approved).
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SIST EN ISO 8871-2:2020
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SIST EN ISO 8871-2:2020
INTERNATIONAL STANDARD ISO 8871-2:2020(E)
Elastomeric parts for parenterals and for devices for
pharmaceutical use —
Part 2:
Identification and characterization
1 Scope
This document specifies identification and characterization procedures applicable to elastomeric parts
including coated stoppers used for drug containers and medical devices.
The physical and chemical test procedures specified in this document permit the determination of
the typical characteristics of elastomeric parts including coatings and surface treatments and can
serve as a basis for agreements between manufacturer and user regarding the product consistency in
subsequent supplies. Depending upon the type of elastomer and its application, an appropriate set of
tests is selected.
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 247-1:2018, Rubber — Determination of ash — Part 1: Combustion method
ISO 2781:2018, Rubber, vulcanized or thermoplastic — Determination of density
ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 1: Extractables
in aqueous autoclavates
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
barrier coating
layer of a different polymer completely or partly covering the elastomeric part to reduce migration,
permeation and/or interactions of substances of rubber component to drug product and vice versa
Note 1 to entry: The coating can be applied by different techniques, such as spraying, tumbling or vapour-
depositing a liquid or vapour onto the rubber component or laminating a film onto the elastomeric surface during
the moulding process.
Note 2 to entry: The presence of the coating can be verified by using the test method described in Annex H.
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
3.2
elastomer
base polymer that is converted into rubber by vulcanization
3.3
lubrication coating
layer of a different polymer completely or partly covering the elastomeric part to support functionality
in the final container closure system
Note 1 to entry: Certain lubrication coatings can also be used to eliminate the need for silicone oil in the container
closure system and/or enhancing other functionalities, such as gliding force, break loose force or removal force.
Note 2 to entry: The coating can be applied by different techniques, such as spraying, tumbling or vapour-
depositing a liquid or vapour onto the rubber component or laminating a film onto the elastomeric surface.
3.4
rubber
vulcanized material obtained by crosslinking of elastomer
[SOURCE: ISO 11999-1:2015 3.75, modified]
3.5
surface treatment
treatment of the surface of rubber by physical or chemical means to get desired properties
EXAMPLE Siliconization, chlorination.
Note 1 to entry: Surface treatments are applied to avoid sticking together and enhance machinability on
processing lines.
4 Tests
4.1 General
Rubber is a complex material and it is not generally definable. The only property which all elastomeric
materials have in common is a special type of resilience or elasticity. When a strip of rubber is stretched,
it will extend by up to many times its original length without breaking. On release of the stretching
force, it snaps back to its original size and shape virtually unaltered. Similarly, one can squeeze it, twist
it or distort it in any direction comparatively easily, and it will virtually spring back again to its original
shape unchanged.
Owing to its three-dimensional network, achieved by chemical cross-linking of the elastomer during
vulcanization, rubber is practically insoluble in solvents such as tetrahydrofuran, although considerable
reversible swelling may occur; this characteristic differentiates rubber from pseudo-elastic materials,
such as poly(vinyl chloride) and certain thermoplastic elastomers.
In view of the complexity of rubber, a set of tests is needed for reliable identification.
The manufacturer shall guarantee that all elastomeric parts of current supplies have been produced
from the same formulation and that they exhibit the same characteristics as the initially supplied
samples.
4.2 Hardness
Hardness shall be determined in accordance with ISO 48-4.
4.3 Density
Density shall be determined in accordance with the procedure described in ISO 2781:2018, Clause 4,
method A.
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
4.4 Ash
The inorganic residue after combustion shall be determined as described in ISO 247-1:2018, 4.1,
method A.
4.5 Infrared spectrum
4.5.1 Material
One method to create a fingerprint of a rubber material is to record an infrared (IR) spectrum. The two
common methods for obtaining an IR spectrum of a rubber material are pyrolysis IR and surface IR/
ATR (attenuated total reflectance)-technique.
The pyrolysis IR can be obtained as described in Annex A. Alternatively, an aliquot of the pyrolysate can
be brought on an ATR crystal of an FTIR-spectrometer as described in Annex H. The surface IR/ATR can
be obtained as described in Annex H. The spectra should be compared with a spectrum obtained by the
same IR method on a reference sample of the material.
In practice, pyrolysis IR requires a time-consuming sample preparation. In addition, it needs the
cautious handling of hazardous vapours and oils.
In contrast to this, the surface IR/ATR offers the possibility to obtain a fingerprint from an elastomeric
part with minimum or no sample preparation.
4.5.2 Coating
The presence of a coating (barrier and lubrication coating) can be verified by comparing FTIR spectra
of the surface and of the core material of the product (see Annex H). For measuring the coating, the
samples do not need to be cut.
4.6 Compression set
The compression set indicates the degree of permanent deformation remaining after compression
at a constant deformation and defined temperature for a defined time. The compression set can be
determined in accordance with Annex B.
4.7 Swelling
Elastomeric materials are subject to varying degrees of swelling when exposed to organic solvents.
The degree of volume and/or mass increase is primarily influenced by the type of elastomer. Swelling
requires special care when the rubber components are in contact with emulsions or oily vehicles.
The relevant procedure is specified in Annex C.
4.8 Development of a fingerprint by gas chromatography
The elastomeric materials under examination are extracted in a solvent which does not dissolve but
might swell the rubber. The extract is injected into a gas chromatograph. The chromatogram obtained
exhibits a typical profile and can be used as a fingerprint for identification purposes. Furthermore,
GC-coupling techniques, for example gas chromatography – mass spectrometry (GC-MS), may provide
additional information about the composition of the extract.
The relevant procedure is specified in Annex D.
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
4.9 Detection of volatile substances by gas chromatography
Elastomeric materials may release volatile substances. These may originate from one of the following
categories of material:
— oligomers or process aids present in the base polymer;
— stabilizers or antioxidants;
— softeners.
The relevant procedure is specified in Annex E.
4.10 Determination of residual moisture
While undergoing treatments which are typical in the pharmaceutical industry, elastomeric parts can
absorb moisture in considerable quantities. During storage of the pharmaceutical product, the trapped
moisture may be released and absorbed by the pharmaceutical product, thus reducing its effectiveness
(critical case: Iyophilized drugs). The nature of the absorption and desorption processes is affected by
the composition of the rubber, the type of treatment (e.g. steam autoclaving) and the efficiency of any
subsequent drying process.
The relevant procedure is specified in Annex F.
4.11 Determination of fingerprint by thermogravimetric analysis (TGA)
Elastomeric parts are composed of components which can be classified relative to their performance
under thermal treatment, as follows:
— base polymers;
— inorganic fillers;
— substances volatile at elevated temperatures;
— carbon black.
The relevant procedure is specified in Annex G.
4.12 Determination of extractables in aqueous autoclavates
Elastomeric materials may release substances of undetermined nature in water. For the general
assessment of the chemical cleanliness of closures ISO 8871-1 applies.
5 Preparation of samples for testing
5.1 Treatment before testing
The various test procedures may require different pretreatments, see Annexes A to H.
It is generally assumed that samples of rubber parts will be provided in a clean state in accordance with
the state of the art. In order to avoid contamination, they shall be contained in a suitable packaging. Any
particular treatment or method of packaging to be carried out by the manufacturer shall be subject to
agreement between the manufacturer and the customer.
5.2 Number of samples needed for the tests
Due to the large number of tests in this document and their complexity, usually not all of the tests are
performed in each investigation. For this reason, the number of samples needed shall be agreed on
4 © ISO 2020 – All rights reserved
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
between the manufacturer and the test laboratory. Each annex specifies the number of samples that are
needed to perform that specific test.
6 Reagents and materials
6.1 Use only reagents of recognized analytical grade, for example water Grade 1 or 2 of ISO 3696 or
any comparable water quality according to current USP and Ph Eur.
6.2 All glass equipment shall be made from borosilicate glass.
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
Annex A
(informative)
Identification of elastomeric material by pyrolysis IR
A.1 General
When rubber parts are exposed to dry heat with restricted access to oxygen, the elastomeric matrix is
thermally disintegrated and the rubber is converted into polymer fragments which appear in the form
of vapour or oils of various viscosities.
These oily products are used to produce an IR spectrum which can serve to identify the original rubber
material.
A.2 Reagents and materials
A.2.1 Dry, filtered acetone, to clean the potassium bromide (KBr) discs.
A.2.2 Indicator paper.
A.2.3 Copper wire.
A.2.4 Acetone.
A.2.5 Trichloromethane.
A.2.6 Sodium sulfate, anhydrous.
A.3 Apparatus
−1 −1
A.3.1 IR spectrometer, to produce IR spectra in the range from 700 cm to 3 800 cm and from 0 %
to 100 % transmission.
A.3.2 KBr discs, including spacers and clamps.
A.3.3 Desiccator.
A.3.4 Bunsen burner.
A.3.5 Test tubes, for the pyrolysis process.
A.3.6 Soxhlet extraction apparatus (optional).
A.4 Sample preparation
Cut about 3 g of a rubber part into pieces of about 3 mm × 3 mm.
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SIST EN ISO 8871-2:2020
ISO 8871-2:2020(E)
Optionally, extract the rubber pieces thus produced with acetone in a Soxhlet extractor under reflux
for 8 h.
A.5 Pyrolysis
Place 0,2 g to 2 g of the rubber pieces in a test tube. Heat with a bunsen burner, carefully driving off
any water which may initially condense above the sample. Subsequently, with the test tube in a nearly
vertical position, expose the rubber pieces to the blue area of the flame. The pyrolysis products
condense as an oil in the cool zone of the test tube. During the pyrolysis, the pH of the vapour released
may be checked with wet indicator paper. An acidic reaction indicates the presence of halogen in the
rubber [parallel to this pH check, a Be
...
SLOVENSKI STANDARD
oSIST prEN ISO 8871-2:2019
01-april-2019
Deli iz elastomera za parenteralne farmacevtske oblike - 2. del: Identifikacija in
opredelitev (ISO/DIS 8871-2:2019)
Elastomeric parts for parenterals and for devices for pharmaceutical use - Part 2:
Identification and characterization (ISO/DIS 8871-2:2019)
Elastomere Teile für Parenteralia und für Geräte zur pharmazeutischen Verwendung -
Identifizierung und Charakterisierung (ISO/DIS 8871-2:2019)
Éléments en élastomère pour administration parentérale et dispositifs à usage
pharmaceutique - Partie 2: dentification et caractérisation (ISO/DIS 8871-2:2019)
Ta slovenski standard je istoveten z: prEN ISO 8871-2
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
oSIST prEN ISO 8871-2:2019 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 8871-2:2019
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oSIST prEN ISO 8871-2:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 8871-2
ISO/TC 76 Secretariat: DIN
Voting begins on: Voting terminates on:
2019-02-14 2019-05-09
Elastomeric parts for parenterals and for devices for
pharmaceutical use —
Part 2:
Identification and characterization
ICS: 11.040.20
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 8871-2:2019(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2019
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oSIST prEN ISO 8871-2:2019
ISO/DIS 8871-2:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019
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
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
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oSIST prEN ISO 8871-2:2019
ISO/DIS 8871-2:2019(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Tests . 2
4.1 General . 2
4.2 Hardness . 2
4.3 Density . 2
4.4 Ash . 3
4.5 Infra-red spectrum . 3
4.5.1 Material . 3
4.5.2 Coating . 3
4.6 Compression set . . 3
4.7 Swelling . 3
4.8 Development of a fingerprint by gas chromatography . 3
4.9 Detection of volatile substances by gas chromatography . 3
4.10 Determination of residual moisture . 4
4.11 Determination of fingerprint by thermogravimetric analysis (TGA) . 4
4.12 Determination of extractables in aqueous autoclavates . 4
5 Preparation of samples for testing . 4
5.1 Treatment before testing . 4
5.2 Number of samples needed for the tests . 4
6 Reagents and materials . 5
Annex A (informative) Identification of elastomeric material by pyrolysis IR .6
Annex B (informative) Determination of compression set . 8
Annex C (informative) Swelling behaviour in oils .10
Annex D (informative) Development of a fingerprint by gas chromatography .12
Annex E (informative) Analysis of volatile components by headspace gas chromatography .14
Annex F (informative) Determination of residual moisture .16
Annex G (informative) Determination of a fingerprint by thermal gravimetry (TG) .17
Annex H (informative) Determination of the elastomer identity and verification of the
presence of a coating by surface infrared spectroscopy(ATR, attenuated total reflection) 21
Bibliography .23
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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 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 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 second edition cancels and replaces the first edition (ISO 8871-2:2003), which has been technically
revised.
The main changes compared to the previous edition are as follows:
— expand the scope about including coated stoppers,
— addition of terms and definitions,
— addition of clause H.6 Interpretation of results for ATR.
A list of all parts in the ISO 8871- 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.
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Introduction
The elastomeric parts specified in the various parts of this International Standard are produced from a
material which is usually called “rubber”. However, rubber is not a unique entity, since the composition
of rubber materials may vary considerably. The base elastomer and the type of vulcanization have a
major influence on the principle characteristics of an individual rubber material, as do additives such
as fillers, softeners and pigments. These may have a significant effect on the overall properties. The
effectiveness, purity, stability and safe handling of a drug preparation may be affected adversely during
manufacture, storage and administration if the rubber part used has not been properly selected and
validated (approved).
Polymer coatings or films are often applied to either entire or partial surface(s) of a rubber component
to impart certain physical or chemical properties. The methods in this document enable determination
of the presence and coverage/continuity of such surface treatments on a rubber component. Evaluation
of the actual properties intended to be provided by these surface treatments is beyond the scope and
covered elsewhere, in 8871 or other ISO documents.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 8871-2:2019(E)
Elastomeric parts for parenterals and for devices for
pharmaceutical use —
Part 2:
Identification and characterization
1 Scope
This document specifies evaluation procedures applicable to elastomeric parts including coated
stoppers used for drug containers and medical devices in order to guarantee the product identity.
The physical and chemical test procedures specified in this document permit the determination
of the typical characteristics of elastomeric parts, and can serve as a basis for agreements between
manufacturer and user regarding the product consistency in subsequent supplies. An appropriate set of
tests is selected, depending upon the type of elastomer and its application.
This document does not specify other requirements for elastomeric parts. These are laid down in the
relevant product standards.
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 48, Rubber, vulcanized or thermoplastic — Determination of hardness (hardness between 10 IRHD and
100 IRHD)
ISO 247:2006, Rubber — Determination of ash
ISO 2781:2018, Rubber, vulcanized or thermoplastic — Determination of density
ISO 8871-1, Elastomeric parts for parenterals and for devices for pharmaceutical use — Part 1: Extractables
in aqueous autoclavates
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
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
3.1
barrier coating
layer of a different polymer completely or partly covering the elastomeric part to reduce migration,
permeation, interactions of substances of rubber component to rubber product and vice versa
Note 1 to entry: The coating can be applied by different techniques, e.g. spraying, tumbling, or vapor-depositing a
liquid or vapor onto the rubber component or laminating a film onto the elastomeric surface during the moulding
process.
Note 2 to entry: The presence of the coating can be verified by using the test method described in Annex H.
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3.2
elastomer
material with elastic properties
3.3
lubrication coating
layer of a different polymer completely or partly covering the elastomeric part to support functionality
in the final container system
Note 1 to entry: Certain lubrication coatings can also be used to eliminate the need of silicone oil in the container
closure system and/or enhancing other functionalities e.g. gliding force, break loose force, removal force.
Note 2 to entry: The coating can be applied by different techniques, e.g. spraying, tumbling, or vapor-depositing a
liquid or vapor onto the rubber component or laminating a film onto the elastomeric surface.
3.4
rubber
elastic substance obtained by crosslinking of polyisoprene or synthetic unsaturated polymers
3.5
surface treatment
any extraneous material placed on any portion of the external surface of the elastomer to produce the
desired properties.
Note 1 to entry: Surface treatments (e.g. siliconization) are applied to avoid sticking together and enhance
machineability on processing lines.
4 Tests
4.1 General
Rubber is a complex material and not generally definable. The only property which all elastomeric
materials have in common is a special type of resilience or elasticity. When a strip of rubber is stretched,
it will extend by up to many times its original length without breaking. On release of the stretching
force, it snaps back to its original size and shape virtually unaltered. Similarly, one can squeeze it, twist
it or distort it in any direction comparatively easily, and it will spring back again to its original shape
unchanged.
Owing to its three-dimensional network, achieved by chemical cross-linking of the polymer chains
during vulcanization, rubber is practically insoluble in solvents such as tetrahydrofuran, although
considerable reversible swelling may occur; this characteristic differentiates rubber from pseudo-
elastic materials, such as poly(vinyl chloride) and certain thermoplastic elastomers.
In view of the complexity of rubber, the identity of a given elastomeric material cannot be verified just
by applying a single physical or chemical test, and a set of tests is needed for reliable identification.
The manufacturer shall guarantee that all elastomeric parts of current supplies have been produced
from the same formulation and that they exhibit the same characteristics as the samples which have
been given to the user first and the suitability of which has been proved.
4.2 Hardness
Hardness shall be determined in accordance with ISO 48.
4.3 Density
Density shall be determined in accordance with the procedure described in ISO 2781:2018, Clause 4,
method A.
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4.4 Ash
The inorganic residue after combustion shall be determined as described in ISO 247:2006, 3.1, method A.
4.5 Infra-red spectrum
4.5.1 Material
A very simple method to create a fingerprint of a rubber material is to record an infrared (IR) spectrum.
The two common methods for obtaining an IR spectrum of a rubber material are pyrolysis IR and
surface IR/ATR (attenuated total reflectance)-technique.
The pyrolysis IR can be obtained as described in Annex A. The surface IR/ATR can be obtained as
described in Annex H. The spectra should be compared to a spectrum obtained by the same IR-method
on a reference sample of the material.
In practice, pyrolysis IR requires a time-consuming sample preparation and in addition needs the
cautious handling of hazardous vapours and oils.
In contrast to this, the surface IR/ATR offers the possibility to obtain a fingerprint from an elastomeric
part with minimum or no sample preparation.
4.5.2 Coating
The presence of a coating can be verified by comparing FTIR spectra of the surface and the material
(see Annex H). For measuring the coating the samples do not need to be cut.
4.6 Compression set
The compression set indicates the degree of permanent deformation remaining after compression
at a constant deformation and defined temperature for a defined time. The compression set shall be
determined in accordance with Annex B.
4.7 Swelling
Elastomeric materials are subject to varying degrees of swelling when exposed to organic solvents;
the degree of volume and/or mass increase is primarily influenced by the type of elastomer. Swelling
requires special care when the rubber components are in contact with emulsions or oily vehicles.
The relevant procedure is specified in Annex C.
4.8 Development of a fingerprint by gas chromatography
The elastomeric materials under examination are extracted in a solvent, which does not dissolve but
might swell the rubber. The extract is injected into a gas chromatograph. The chromatogram obtained
exhibits a typical profile and can be used as a fingerprint for identification purposes. Furthermore,
GC-coupling techniques, e.g. GC-MS, may provide additional information about the composition of the
extract.
The relevant procedure is specified in Annex D.
4.9 Detection of volatile substances by gas chromatography
Elastomeric materials may release volatile substances. These may originate from one of the following
categories of material:
— oligomers or process aids present in the base polymer;
— stabilizers or antioxidants;
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— softeners.
The relevant procedure is specified in Annex E.
4.10 Determination of residual moisture
During treatments typical for the pharmaceutical industry, elastomeric parts can absorb moisture in
considerable quantities. During storage of the drug unit, the trapped moisture may be released and
absorbed by the drug product, thus reducing the effectiveness of the drug (critical case: Iyophilized
drugs). The nature of the absorption and desorption processes is affected by the composition of the
rubber, the type of treatment (e.g. steam autoclaving) and the efficiency of any subsequent drying
process.
The relevant procedure is specified in Annex F.
4.11 Determination of fingerprint by thermogravimetric analysis (TGA)
Elastomeric parts are composed of components which can be classified relative to their performance
under thermal treatment, as follows:
— base polymers;
— inorganic fillers;
— substances volatile at elevated temperatures;
— carbon black.
The relevant procedure is specified in Annex G.
4.12 Determination of extractables in aqueous autoclavates
Elastomeric materials may release substances of undetermined nature in water. For the general
assessment of the chemical cleanliness of closures, the determination of overall parameters such as
oxidizable materials and electrical conductivity can be used.
The relevant test procedures are specified in ISO 8871-1.
5 Preparation of samples for testing
5.1 Treatment before testing
Since the various test procedures may require different pretreatments, such treatment is specified in
each annex.
It is generally assumed that samples of rubber parts will be provided in a clean state in accordance with
the state of the art. In order to avoid recontamination, they shall be contained in protective packaging.
Any particular treatment or method of packaging to be carried out by the manufacturer shall be subject
to agreement between the manufacturer and the customer.
5.2 Number of samples needed for the tests
Due to the large number of tests in this part of ISO 8871 and their complexity, usually not all of the tests
are performed in each investigation. For this reason, the number of samples needed shall be agreed on
between the manufacturer and the test laboratory. Each annex specifies the number of samples which
are necessary to perform that specific test.
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6 Reagents and materials
5.1 Use only reagents of recognized analytical grade and purified water prepared by distillation or by
other suitable means. The conductivity of the water used shall not exceed 3,0 µS/cm.
NOTE Purified water as specified by various national pharmacopoeias corresponds to grade 1 or 2 of
ISO 3696.
5.2 All glass equipment shall be made from borosilicate glass.
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Annex A
(informative)
Identification of elastomeric material by pyrolysis IR
A.1 General
When rubber parts are exposed to dry heat with restricted access to oxygen, the elastomeric matrix is
thermally disintegrated and the rubber is converted into polymer fragments which appear in the form
of vapour or oils of various viscosities.
These oily products are used to produce an IR spectrum which can serve to identify the original rubber
material.
A.2 Reagents and materials
A.2.1 Dry, filtered acetone, to clean the KBr discs.
A.2.2 Indicator paper.
A.2.3 Copper wire.
A.2.4 Acetone.
A.2.5 Trichloromethane.
A.2.6 Sodium sulfate, anhydrous.
A.3 Apparatus
−1 −1
A.3.1 IR spectrometer, to produce IR spectra in the range from 400 cm to 4 000 cm and from 0 %
to 100 % transmission.
A.3.2 Potassium bromide (KBr) discs, including spacers and clamps.
A.3.3 Desiccator.
A.3.4 Bunsen burner.
A.3.5 Test tubes, for the pyrolysis process.
A.3.6 Soxhlet extraction apparatus (optional).
A.4 Sample preparation
Cut about 3 g of a rubber part into pieces of about 3 mm × 3 mm.
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Optionally, extract the rubber pellets thus produced with acetone in a Soxhlet extractor under reflux
for 8 h.
A.5 Pyrolysis
Place 0,2 g to 2 g of the rubber pellets in a test tube. Heat with a bunsen burner, carefully driving off
any water which may initially condense above the sample. Subsequently, with the test tube in a nearly
vertical position, expose the rubber pellets to the blue area of the flame. The pyrolysis products
condense as an oil in the cool zone of the test tube. During the pyrolysis, the pH of the vapour released
may be checked with wet indicator paper. An acidic reaction indicates the presence of halogen in the
rubber [parallel to this pH check, a Beilstein (copper wire) test can be performed].
The reproducibility of the procedure specified above is good enough to obtain spectra for qualitative
interpretation. The pyrolysis does not have to be performed under nitrogen at constant temperature.
A.6 Recording the spectrum
A.6.1 The liquid pyrolysis product obtained as described in Clause A.5 is best dried while still in the test
tube over Na SO in a desiccator. Then place it between two clean polished KBr discs. Usually, a thin layer
2 4
(up to 0,03 mm) is sufficient to give a transmission spectrum in the range from 0 % to 80 %. If necessary,
produce a thicker layer of pyrolysed material by using suitable spacers. The pyrolysed material should be
evenly distribution without any included air bubbles.
−1 −1
A.6.2 Record the spectrum as a transmission spectrum ranging from 400 cm to 4 000 cm .
A.7 Interpretation
A.7.1 General
The pyrolysis process is a very complex one, which means that no two spectra produced will be
identical, even if the sample preparation is the same. For this reason, particular features of the spectrum
which are typical of the type of rubber are selected for identification purposes. Since the influence of
oxygen during the pyrolysis cannot be excluded, those features of the spectrum produced by oxidation
products (alcohols, ethers, aldehydes and acids) are disregarded.
A.7.2 Expression of results
Taking into consideration the limitations set out in A.7.1, compare the spectrum obtained with reference
spectra at the wavelengths characteristic of the features of interest.
Record the result as the spectrum obtained, together with the results of the analysis of the spectrum.
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Annex B
(informative)
Determination of compression set
B.1 General
Determination of the compression set provides information about the performance of elastomeric
materials when exposed to constant deformation over an extended time at room temperature or at
elevated temperature. For details, see ISO 815.
B.2 Apparatus
B.2.1 Compression apparatus, consisting of two or more parallel, flat, highly polished chromium-
plated steel or stainless-steel plates between the faces of which the test pieces are compressed. The
surface roughness Ra of the compression plates shall not exceed 0,4 µm. The plates shall be sufficiently
rigid to withstand the stress produced without bending, and of sufficient size to ensure that all the
compressed test pieces remain within the area of the plates. The plates shall be held together by bolts
of suitable size. Steel spacers, preferably in the form of rings, of thickness between 4,7 mm and 4,8 mm,
shall be used to ensure the required compression. The spacers shall be of such a width that contact with
the compressed test pieces is avoided. While the spacer thickness may be between 4,7 mm and 4,8 mm,
the thickness of the spacers used in a series of related tests shall not vary by more than 0,01 mm.
B.2.2 Oven: Any well-designed, uniformly heated air oven capable of maintaining the compression
apparatus and test pieces at the required temperature within the tolerance limits given in Clause B.4 is
suitable.
B.3 Samples
As the test cannot be performe
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