EN ISO 10993-14:2009

Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14:2001)

2010-01-06 SJ: Std cited under 98/79/EC through publication C293 on 2009-12-02, in error (should only be cited under 93/42). OJEU flag removed as well as OJEU publication data.

Biologische Beurteilung von Medizinprodukten - Teil 14: Qualitativer und quantitativer Nachweis von keramischen Abbauprodukten (ISO 10993-14:2001)

Keramiken (einschließlich Glas) zum Zweck der quantitativen Bestimmung fest. Er gibt auch eine Anleitung
zur analytischen Untersuchung dieser Lösungen zur qualitativen Bestimmung der Abbauprodukte. Wegen der
Allgemeingültigkeit dieses Teils der Normenserie ISO 10993 sollte die Anwendung vorhandener
produktspezifischer Normen, die die Bildung von Abbauprodukten unter mehr anwendungsbezogenen
Bedingungen behandeln, bevorzugt in Erwägung gezogen werden.
Dieser Teil der ISO 10993 berücksichtigt nur die Abbauprodukte, die durch einen chemischen Zerfall der
keramischen Werkstoffe während einer Prüfung in vitro entstehen. Ein Abbau durch mechanische Belastung
oder äußere Energie wird in diesem Teil von ISO 10993 nicht behandelt. Es wird darauf hingewiesen, dass
ISO 6872 und ISO 9693 zwar Prüfungen des chemischen Abbaus enthalten, sie jedoch nicht die Analyse der
Abbauprodukte behandeln.
Wegen der Verschiedenartigkeit der in Medizinprodukten verwendeten keramischen Werkstoffe und der
unterschiedlichen Anforderungen an die Genauigkeit und Präzision der Ergebnisse werden keine spezifischen
analytischen Techniken festgelegt. Weiterhin gibt dieser Teil von ISO 10993 keine spezifischen
Anforderungen für vertretbare Konzentrationen von Abbauprodukten an.
Obgleich diese Werkstoffe für die biomedizinische Anwendung vorgesehen sind, wird die biologische Aktivität
von deren Abbauprodukten in diesem Teil der ISO 10993 nicht behandelt.

Évaluation biologique des dispositifs médicaux - Partie 14: Identification et quantification des produits de dégradation des céramiques (ISO 10993-14:2001)

La présente partie de l'ISO 10993 spécifie deux méthodes permettant d'obtenir des solutions de produits de dégradation à partir des céramiques (dont les verres) dans un but de quantification. Elle donne également des lignes directrices pour l'analyse de ces solutions afin d'identifier les produits de dégradation. Etant donné la nature générale de la présente partie de l'ISO 10993, il convient de prendre en compte en premier lieu les normes spécifiques aux produits qui, lorsqu'elles existent, abordent la formation de produits de dégradation dans des conditions d'utilisation plus pertinentes La présente partie de l'ISO 10993 aborde seulement les produits de dégradation générés par dissociation chimique des céramiques lors d'essais in vitro. Aucune dégradation due à une contrainte mécanique ou une énergie externe ne relève de la présente partie de l'ISO 10993. Alors que l'ISO 6872 et l'ISO 9693 sont des essais de dégradation chimique, elles ne traitent pas de l'analyse des produits de dégradation.  Étant donné la gamme des céramiques utilisées dans les dispositifs médicaux et les différentes exigences d'exactitude et de fidélité des résultats, aucune technique d'analyse spécifique n'est identifiée. De plus, la présente partie de l'ISO 10993 ne fait état d'aucune exigence spécifique relative à des niveaux acceptables de produits de dégradation.  Bien que ces matériaux soient conçus pour des applications biomédicales, l'activité biologique de ces produits de dégradation ne fait pas l'objet de la présente partie de l'ISO 10993.

Biološko ovrednotenje medicinskih pripomočkov - 14. del: Prepoznavanje in ugotavljanje količine razgradnih produktov iz keramike (ISO 10993-14:2001)

General Information

• Status: Published
• Publication Date: 28-Apr-2009
• Withdrawal Date: 20-Mar-2010
• ICS: 11.100 - Laboratory medicine
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Drafting Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Current Stage: 6060 - Definitive text made available (DAV) - Publishing
• Start Date: 29-Apr-2009
• Completion Date: 29-Apr-2009
• Directive: 2007/47/EC - Directive 2007/47/EC of the European Parliament and of the council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Directive: 98/79/EC - Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: SIST EN ISO 10993-14:2009 - Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14:2001)

Relations

• Replaces: EN ISO 10993-14:2001 - Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14:2001)
• Effective Date: 06-May-2009

Overview

EN ISO 10993-14:2009 (identical to ISO 10993-14:2001) is part of the ISO 10993 series on the biological evaluation of medical devices. It defines procedures to identify and quantify degradation products from ceramics (including glasses) by in vitro chemical dissolution. The standard provides two complementary test methods - an extreme solution test (low pH, worst‑case screen) and a simulation solution test (representative of commonly encountered in vivo pH) - and guidance on analysing the resulting solutions (filtrate) to support risk assessment and subsequent biological safety evaluations under ISO 10993-1.

Key topics and requirements

• Scope
  • Applies to ceramics used in medical devices (bulk, granular, blank discs) and to degradation produced by chemical dissociation in aqueous in vitro tests.
  • Excludes degradation induced by mechanical stress, external energy, or biological agents (enzymes/proteins).
• Two test approaches
  • Extreme solution test: low‑pH, worst‑case screening to reveal likely dissolution products.
  • Simulation solution test: mimics more typical in vivo aqueous conditions to produce realistic degradation profiles.
• Sample handling & outputs
  • Distinguishes filtrate (solution passing the filter) and retentate (undissolved solids).
  • Guidance on what chemicals/elements to analyse and on method sensitivity; no single analytical technique is mandated.
• Analytical guidance
  • The standard does not prescribe specific instruments or detection limits - laboratories select appropriate methods based on the ceramic type and required accuracy/precision.
• Reporting
  • Specifies content to include in the test report to support traceability and risk assessment.
• Regulatory linkage
  • Adopted as a CEN standard and intended to support Essential Requirements of EU Directive 93/42/EEC for medical devices (see informative Annex ZA).

Applications and who uses it

• Medical device manufacturers developing ceramic/dental/implantable components who need to characterise potential leachables and degradation products.
• Biocompatibility engineers and toxicologists conducting chemical characterisation and preparing safety dossiers.
• Analytical laboratories selecting dissolution protocols and analytical methods (e.g., ICP, AAS, chromatography) appropriate to the material.
• Regulatory affairs specialists using standardised test data to demonstrate conformity with ISO 10993 series and EU medical device requirements.
• Risk assessors who use identified/quantified degradation products as inputs to biological safety and allowable‑limit evaluations.

Related standards

• ISO 10993-1 (general biological evaluation)
• ISO 10993-9 (framework for identification/quantification of potential degradation products)
• Other ISO 10993 parts addressing polymers, metals and toxicokinetics (for complementary testing and risk assessment)

Keywords: EN ISO 10993-14, ISO 10993-14, biological evaluation, degradation products from ceramics, ceramic degradation testing, extreme solution test, simulation solution test, medical device biocompatibility, leachables, 93/42/EEC.

Standards Content (Sample)

SLOVENSKI STANDARD
01-julij-2009
1DGRPHãþD
SIST EN ISO 10993-14:2002
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO3UHSR]QDYDQMHLQ
XJRWDYOMDQMHNROLþLQHUD]JUDGQLKSURGXNWRYL]NHUDPLNH,62
Biological evaluation of medical devices - Part 14: Identification and quantification of
degradation products from ceramics (ISO 10993-14:2001)
Biologische Beurteilung von Medizinprodukten - Teil 14: Qualitativer und quantitativer
Nachweis von keramischen Abbauprodukten (ISO 10993-14:2001)
Evaluation biologique des dispositifs médicaux - Partie 14 : Identification et quantification
des produits de dégradation des céramiques (ISO 10993-14:2001)
Ta slovenski standard je istoveten z: EN ISO 10993-14:2009
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 10993-14
NORME EUROPÉENNE
EUROPÄISCHE NORM
April 2009
ICS 11.100.20 Supersedes EN ISO 10993-14:2001
English Version
Biological evaluation of medical devices - Part 14: Identification
and quantification of degradation products from ceramics (ISO
10993-14:2001)
Évaluation biologique des dispositifs médicaux - Partie 14: Biologische Beurteilung von Medizinprodukten - Teil 14:
Identification et quantification des produits de dégradation Qualitativer und quantitativer Nachweis von keramischen
des céramiques (ISO 10993-14:2001) Abbauprodukten (ISO 10993-14:2001)
This European Standard was approved by CEN on 12 April 2009.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN Management Centre or to any CEN member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2009 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-14:2009: E
worldwide for CEN national Members.

Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices .4

Foreword
The text of ISO 10993-14:2001 has been prepared by Technical Committee ISO/TC 194 “Biological evaluation
of medical devices” of the International Organization for Standardization (ISO) and has been taken over as EN
ISO 10993-14:2009 by Technical Committee CEN/TC 206 “Biological evaluation of medical devices” the
secretariat of which is held by NEN.
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 October 2009, and conflicting national standards shall be withdrawn at
the latest by March 2010.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 10993-14:2001.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive 93/42/EEC on
Medical Devices.
For relationship with the EU Directive, see informative Annex ZA, which is an integral part of this document.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 10993-14:2001 has been approved by CEN as a EN ISO 10993-14:2009 without any
modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential Requirements of
EU Directive 93/42/EEC on Medical Devices

This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Communities under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in table ZA confers, within the limits of the scope of this standard, a presumption of conformity
with the corresponding Essential Requirements of that Directive and associated EFTA regulations.
Table ZA — Correspondence between this European Standard and Directive 93/42/EEC on medical
devices
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) of Qualifying remarks/Notes
EN Directive 93/42/EEC
4, 5, 6
Annex I:
7.1, 7.2, 7.5
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
INTERNATIONAL ISO
STANDARD 10993-14
First edition
2001-11-15
Biological evaluation of medical devices —
Part 14:
Identification and quantification of
degradation products from ceramics
Évaluation biologique des dispositifs médicaux —
Partie 14: Identification et quantification des produits de dégradation des
céramiques
Reference number
ISO 10993-14:2001(E)
©
ISO 2001
ISO 10993-14:2001(E)
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ii © ISO 2001 – All rights reserved

ISO 10993-14:2001(E)
Contents Page
Foreword.iv
Introduction.vi
1 Scope .1
2 Normative references .1
3 Terms and definitions .2
4 Test procedures.2
4.1 Principle.2
4.2 Testing of dental devices.2
4.3 General testing techniques.3
4.4 Extreme solution test .4
4.5 Simulation solution test .6
5 Analysis of filtrate.9
5.1 General.9
5.2 Choice of chemicals or elements to be analysed.9
5.3 Sensitivity of the analysis method.9
6 Test report .9
Bibliography.11
ISO 10993-14:2001(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 3.
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 part of ISO 10993 may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights.
International Standard ISO 10993-14 was prepared by Technical Committee ISO/TC 194, Biological evaluation of
medical devices.
ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:
— Part 1: Evaluation and testing
— Part 2: Animal welfare requirements
— Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
— Part 4: Selection of tests for interactions with blood
— Part 5: Tests for in vitro cytotoxicity
— Part 6: Tests for local effects after implantation
— Part 7: Ethylene oxide sterilization residuals
— Part 8: Selection and qualification of reference materials for biological tests
— Part 9: Framework for identification and quantification of potential degradation products
— Part 10: Tests for irritation and delayed-type hypersensitivity
— Part 11: Tests for systemic toxicity
— Part 12: Sample preparation and reference materials
— Part 13: Identification and quantification of degradation products from polymeric medical devices
— Part 14: Identification and quantification of degradation products from ceramics
— Part 15: Identification and quantification of degradation products from metals and alloys
— Part 16: Toxicokinetic study design for degradation products and leachables
iv © ISO 2001 – All rights reserved

ISO 10993-14:2001(E)
— Part 17: Establishment of allowable limits for leachable substances using health-based risk assessment
— Part 18: Chemical characterization of materials
ISO 10993-14:2001(E)
Introduction
This part of ISO 10993 consists of two tests for the biological evaluation of medical devices: an extreme solution
test and a simulation solution test. The extreme solution test is developed as a worst-case environment and the
simulation test is developed as a very common environment.
Degradation products covered by this part of ISO 10993 are formed primarily by dissolution in an aqueous
environment. It is recognized that additional biological factors such as enzymes and proteins can alter the rate of
degradation. Degradation by such outside factors is not addressed in this part of ISO 10993.
It should be kept in mind that a ceramic device might have extraneous chemical phases and/or elements in
extremely minor amounts. Whilst these components might not be named in the original specification, they can often
be suspected by the relationship that the material in question has to other materials and the expected history of the
material’s processing.
Once identified and quantified, the chemical composition of the degradation products form the basis for risk
assessment and, if appropriate, biological safety studies according to the principles of ISO 10993-1.
vi © ISO 2001 – All rights reserved

INTERNATIONAL STANDARD ISO 10993-14:2001(E)
Biological evaluation of medical devices —
Part 14:
Identification and quantification of degradation products from
ceramics
1 Scope
This part of ISO 10993 specifies two methods of obtaining solutions of degradation products from ceramics
(including glasses) for the purposes of quantification. It also gives guidance on the analysis of these solutions in
order to identify the degradation products. Because of the generalized nature of this part of ISO 10993, product
specific standards, when available, that address degradation product formation under more relevant conditions of
use, should be considered first.
This part of ISO 10993 considers only those degradation products generated by a chemical dissociation of
ceramics during in vitro testing. No degradation induced by mechanical stress or external energy is covered. It is
noted that while ISO 6872 and ISO 9693 cover chemical degradation tests, they do not address the analysis of
degradation products.
Because of the range of ceramics used in medical devices and the different requirements for accuracy and
precision of the results, no specific analytical techniques are identified. Further, this part of ISO 10993 provides no
specific requirements for acceptable levels of degradation products.
Although these materials are intended for biomedical applications, the biological activity of these degradation
products is not addressed in this part of ISO 10993.
2 Normative references
The following normative documents contain provisions which, through reference in this text, constitute provisions of
this part of ISO 10993. For dated references, subsequent amendments to, or revisions of, any of these publications
do not apply. However, parties to agreements based on this part of ISO 10993 are encouraged to investigate the
possibility of applying the most recent editions of the normative documents indicated below. For undated
references, the latest edition of the normative document referred to applies. Members of ISO and IEC maintain
registers of currently valid International Standards.
ISO 3310-1, Test sieves — Technical requirements and testing — Part 1: Test sieves of metal wire cloth
ISO 3696, Water for analytical laboratory use — Specification and test methods
ISO 5017, Dense shaped refractory products — Determination of bulk density, apparent porosity and true porosity
ISO 6474, Implants for surgery — Ceramic materials based on high purity alumina
ISO 6872:1995, Dental ceramic
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing
ISO 10993-14:2001(E)
ISO 10993-9, Biological evaluation of medical devices — Part 9: Framework for identification and quantification of
potential degradation products
3 Terms and definitions
For the purposes of this part of ISO 10993, the terms and definitions given in ISO 10993-1 and ISO 10993-9 as well
as the following apply.
3.1
ceramics
typically crystallized materials that are physically nonmetallic and chemically inorganic
3.2
blank disc
noncoated circular plate made of the substrate material to be used in the finished device
3.3
retentate
undissolved solids remaining in the filter paper after filtration
3.4
filtrate
solution which passes through the filter paper
4 Test procedures
4.1 Principle
This part of ISO 10993 consists of two tests. The first test, an extreme solution test conducted at low pH, serves as
a screen for most ceramics for the observation of possible degradation products. The second test simulates a more
fre
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