SIST EN ISO 8871-1:2005

SLOVENSKI STANDARD
01-marec-2005
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Elastomeric parts for parenterals and for devices for pharmaceutical use - Part 1:
Extractables in aqueous autoclavates (ISO 8871-1:2003)
Elastomere Teile für Parenteralia und für Geräte zur pharmazeutischen Verwendung -
Teil 1: Extrahierbare Substanzen in wässrigen Autoklavaten (ISO 8871-1:2003)
Eléments en élastomere pour administration parentérale et dispositifs a usage
pharmaceutique - Partie 1: Substances extractibles par autoclavage en milieu aqueux
(ISO 8871-1:2003)
Ta slovenski standard je istoveten z: EN ISO 8871-1:2004
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 8871-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
September 2004
ICS 11.040.20 Supersedes EN ISO 8871:1997
English version
Elastomeric parts for parenterals and for devices for
pharmaceutical use - Part 1: Extractables in aqueous
autoclavates (ISO 8871-1:2003)
Eléments en élastomère pour administration parentérale et
dispositifs à usage pharmaceutique - Partie 1: Substances
extractibles par autoclavage en milieu aqueux (ISO 8871-
1:2003)
This European Standard was approved by CEN on 15 July 2004.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, 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
© 2004 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 8871-1:2004: E
worldwide for CEN national Members.

Foreword
The text of ISO 8871-1:2003 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 8871-
1:2004 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 March 2005, and conflicting national
standards shall be withdrawn at the latest by March 2005.

This document supersedes EN ISO 8871:1997.

According to the CEN/CENELEC Internal Regulations, the national standards organizations of
the following countries are bound to implement this European Standard: Austria, Belgium,
Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary,
Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,
Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.

Endorsement notice
The text of ISO 8871-1:2004 has been approved by CEN as EN ISO 8871-1:2004 without any
modifications.
NOTE Normative references to International Standards are listed in annex ZA (normative).

Annex ZA
(normative)
Normative references to international publications
with their relevant European publications

This European Standard incorporates by dated or undated reference, provisions from other
publications. These normative references are cited at the appropriate places in the text and the
publications are listed hereafter. For dated references, subsequent amendments to or revisions of
any of these publications apply to this European Standard only when incorporated in it by
amendment or revision. For undated references the latest edition of the publication referred to
applies (including amendments).

NOTE Where an International Publication has been modified by common modifications, indicated
by (mod.), the relevant EN/HD applies.

Publication Year Title EN Year

ISO 8362-2 1988 Injection containers for injectables EN 28362-2 1993
and accessories - Part 2: Closures
for injection vials
INTERNATIONAL ISO
STANDARD 8871-1
First edition
2003-10-01
Elastomeric parts for parenterals and for
devices for pharmaceutical use —
Part 1:
Extractables in aqueous autoclavates
Éléments en élastomère pour administration parentérale et dispositifs à
usage pharmaceutique —
Partie 1: Substances extractibles par autoclavage en milieu aqueux

Reference number
ISO 8871-1:2003(E)
©
ISO 2003
ISO 8871-1:2003(E)
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ii © ISO 2003 — All rights reserved

ISO 8871-1:2003(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope. 1
2 Normative references . 1
3 Classification. 2
4 Requirements . 2
5 Sampling . 2
6 Apparatus and reagents. 3
7 Preparation of test solutions . 4
Annex A (normative) Appearance of solution . 5
Annex B (normative) Acidity or alkalinity . 9
Annex C (normative) Absorbance . 10
Annex D (normative) Reducing substances. 11
Annex E (normative) Extractable heavy metals . 12
Annex F (normative) Extractable zinc . 14
Annex G (normative) Extractable ammonia. 15
Annex H (normative) Residue on evaporation . 16
Annex I (normative) Volatile sulfides .17
Annex J (informative) Conductivity . 18
Bibliography . 19

ISO 8871-1:2003(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 8871-1 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment
for medical and pharmaceutical use.
Together with the other parts (see below), this part of ISO 8871 cancels and replaces ISO 8871:1990, which
has been technically revised.
ISO 8871 consists of the following parts, under the general title Elastomeric parts for parenterals and for
devices for pharmaceutical use:
 Part 1: Extractables in aqueous autoclavates
 Part 2: Identification and characterization
 Part 3: Determination of released-particle count
 Part 4: Biological requirements and test methods
 Part 5: Functional requirements and testing
iv © ISO 2003 — All rights reserved

ISO 8871-1:2003(E)
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).
INTERNATIONAL STANDARD ISO 8871-1:2003(E)

Elastomeric parts for parenterals and for devices for
pharmaceutical use —
Part 1:
Extractables in aqueous autoclavates
1 Scope
1.1 This part of ISO 8871 defines procedures for classifying elastomeric parts for primary packs and
medical devices used in direct contact with preparations for parenteral use, including both aqueous
preparations and dry preparations which have to be dissolved before use.
It specifies a series of comparative test methods for chemical evaluation by the determination of extractables
in aqueous autoclavates (see Clause 4) and describes the various fields of application for elastomeric parts.
Dimensions and functional characteristics are specified in the relevant International Standards. Required
properties as specified in this part of ISO 8871 are regarded as minimum requirements.
1.2 This part of ISO 8871 is applicable for the categories of elastomeric parts given in Clause 3; specific
requirements, however, are laid down in the relevant International Standards dealing with the items or devices
listed in Clause 3.
Elastomeric parts for empty syringes for single use are excluded from the scope of this part of ISO 8871 as
they are not in contact with the injected preparation for a significant length of time.
1.3 Compatibility studies with the intended preparation have to be performed before the approval for final
use can be given; however, this part of ISO 8871 does not specify procedures for carrying out compatibility
studies.
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 8362-2:1988, Injection containers for injectables and accessories — Part 2: Closures for injection vials
ISO 8362-5:1995, Injection containers for injectables and accessories — Part 5: Freeze drying closures for
injection vials
ISO 8536-2:2001, Infusion equipment for medical use — Part 2: Closures for infusion bottles
ISO 8536-6:1995, Infusion equipment for medical use — Part 6: Freeze drying closures for infusion bottles
ISO 11040-2:1994, Prefilled syringes — Part 2: Plungers and discs for dental local anaesthetic cartridges
ISO 11040-5:2001, Prefilled syringes — Part 5: Plungers for injectables
ISO 8871-1:2003(E)
3 Classification
Elastomeric parts exist in various designs and sizes depending on the intended end-use. These parts serve
different purposes depending on the item or device in which they are incorporated. Elastomeric parts have,
therefore, been classified into the following categories:
 elastomeric parts for injection vials (see ISO 8362-2);
 elastomeric parts for infusion bottles (see ISO 8536-2);
 elastomeric parts for prefilled syringes (see ISO 11040-2 and ISO 11040-5);
 elastomeric parts for medical devices for pharmaceutical use (excluding gloves and probes);
 elastomeric parts for freeze-dried products (see ISO 8362-5 and ISO 8536-6).
4 Requirements
4.1 Resistance to steam sterilization
Elastomeric parts shall not lose their required biological, chemical and physical properties after being sterilized
twice in saturated steam at (121 ± 2) °C for 30 min each time.
4.2 Chemical requirements
Elastomeric parts shall comply with the chemical requirements specified in Table 1.
Elastomers are divided into the following types:
 Type I elastomer: this meets the strictest requirements and is the preferred type.
 Type II elastomer: this does not meet these severe requirements as a result of its different chemical
composition which is necessary to give the mechanical properties required for special applications (e.g.
multiple piercing).
The methods to be used to determine the chemical characteristics of the elastomeric parts are specified in
Annex A to Annex J.
5 Sampling
Take a random sample of the elastomeric parts which is representative of each delivery, with the parts in their
original state. The number of elastomeric parts taken shall be as specified in the relevant International
Standards (see Clause 3).
2 © ISO 2003 — All rights reserved

ISO 8871-1:2003(E)
Table 1 — Chemical requirements for testing aqueous autoclavates
Characteristic Requirements Test as described in
Clause/Annex
Turbidity Type l: Not more turbid than reference suspension II A.1
Type Il: Not more turbid than reference suspension III
Colour Type I and II: Not more intensely coloured than reference A.2
solution GY
Acidity/alkalinity Type I and II: B
u 0,3 ml sodium hydroxide solution, c(NaOH) = 0,01 mol/l
or
u 0,8 ml hydrochloric acid, c(HCI) = 0,01 mol/l
Absorbance Type l: u 0,2 AU across the whole range from 220 nm to 360 nm C
Type II: u 4,0 AU across the whole range from 220 nm to 360 nm
Reducing substances Type l: u 3,0 ml sodium thiosulfate solution, D
c(Na S O ) = 0,01 mol/l
2 2 3
Type II: u 7,0 ml sodium thiosulfate solution,
c(Na S O ) = 0,01 mol/l
2 2 3
Extractable heavy metals Type I and II: u 2,0 mg/l E
Extractable zinc Type I and II: u 5,0 mg/l F
Extractable ammonia Type I and II: u 2,0 mg/l G
Residue on evaporation Type I: u 2,0 mg/50 ml H
Type II: u 4,0 mg/50 ml
Volatile sulfides Type I and II: Black stain on acetate paper shall not be larger or I
darker than reference (0,154 mg Na S for every 20 cm of
stopper surface area.)
Conductivity (optional) Type I: u 15 µS/cm J
Type II: u 30 µS/cm
A blank may be prepared where appropriate for system control, but correction of the result using the blank result is only
allowed if mentioned in the corresponding annex.
6 Apparatus and reagents
6.1 Use only reagents of recognized analytical grade. For the preparation of standard solutions, see the
relevant annex.
6.2 Use purified water prepared by distillation or by any other suitable means.
Its conductivity shall be less than 3,0 µS/cm.
NOTE Purified water as specified in various national pharmacopoeias corresponds to grade 1 and grade 2 water as
specified in ISO 3696.
6.3 Glassware shall be made from borosilicate glass.
ISO 8871-1:2003(E)
7 Preparation of test solutions
7.1 Closures shall be processed in the as-delivered condition.
7.2 Place a suitable number of complete elastomeric parts in a wide-necked flask and add 300 ml of
purified water for every 150 cm of surface area of the elastomeric parts. Cover the mouth of the flask, e.g.
with aluminium foil or an inverted borosilicate glass beaker. Weigh the flask plus contents. Heat in an
autoclave so that a temperature of (121 ± 2) °C is reached within 20 min to 30 min and maintain this
temperature for 30 min. Cool to room temperature over about 30 min. Make up to the original mass with
purified water if necessary (if tightly closed containers are not used).
Shake this solution (solution S ) and immediately separate it from the elastomeric parts. Shake solution S
1 1
before each test.
7.3 Prepare a blank solution (solution S ) in the same way as for solution S except that 300 ml of purified
0 1
water are used without the elastomeric parts.
7.4 Use solutions S and S obtained as described to carry out the chemical tests.
1 0
4 © ISO 2003 — All rights reserved

ISO 8871-1:2003(E)
Annex A
(normative)
Appearance of solution
A.1 Turbidity of solution S
A.1.1 General
The determination may be carried out instrumentally using a turbidimeter or by visual comparison.
A.1.2 Visual comparison with standards
A.1.2.1 Reagents
A.1.2.1.1 Hydrazine sulfate solution
Dissolve 1,0 g of hydrazine sulfate in water and dilute to 100 ml with water. Allow to stand for 4 h to 6 h.
A.1.2.1.2 Hexamethylenetetramine solution
Dissolve 2,5 g of hexamethylenetetramine in 25,0 ml of water in a glass-stoppered 100 ml flask.
A.1.2.1.3 Stock suspension
To the solution of hexamethylenetetramine in the flask add 25,0 ml of hydrazine sulfate solution. Mix and allow
to stand for 24 h. This suspension is stable for 2 months, provided it is stored in a glass container free from
surface defects. Discard if the suspension adheres to the glass. Mix well before use.
A.1.2.1.4 Standard suspension
Dilute 15,0 ml of the stock s
...