EN ISO 10993-6:2007

Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6:2007)

This part of ISO 10993 specifies test methods for the assessment of the local effects of an implant material on living tissue, at both the macroscopic and microscopic level.  The test specimen is implanted into a site and tissue appropriate for evaluation of the biological safety of the material. The implant is not intended to be subjected to mechanical or functional loading. The local effects are evaluated by a comparison of the tissue response caused by a test specimen to that caused by materials used in medical devices whose clinical acceptability has been established.  The test methods for local effects after implantation are used to assess subchronic effects (short-term, up to 12 weeks), or chronic effects (long-term, longer than 12 weeks).

Biologische Beurteilung von Medizinprodukten - Teil 6: Prüfungen auf lokale Effekte nach Implantationen (ISO 10993-6:2007)

Dieser Teil von ISO 10993 legt Prüfverfahren fest zur Beurteilung der lokalen Effekte nach der Implantation von Biomaterialien, die zur Verwendung in Medizinprodukten vorgesehen sind.
Dieser Teil von ISO 10993 gilt für Werkstoffe, die
   fest und nicht biologisch abbaufähig;
   abbaufähig und/oder resorbierbar; und
   nicht im festen Zustand sind, wie poröse Werkstoffe, sowie Flüssigkeiten, Pasten und suspendierte Partikel.
Der Prüfkörper wird in eine Stelle und Tierart implantiert, die geeignet ist, die biologische Sicherheit des Werkstoffes zu beurteilen. Diese Implantationsprüfungen sind nicht dazu vorgesehen, die Leistung des Prüfkörpers im Sinne der mechanischen oder funktionellen Belastbarkeit zu ermitteln. Dieser Teil von ISO 10993 kann auch für Medizinprodukte gelten, die dazu vorgesehen sind, bei klinischen Indikationen lokal angewendet zu werden, bei denen die Oberfläche oder Auskleidung einer Körperhöhle geöffnet worden sein kann, um die Reaktionen des lokalen Gewebes zu beurteilen.
Die lokalen Effekte werden durch einen Vergleich der durch einen Prüfkörper hervorgerufenen Gewebsreaktion mit der durch in Medizinprodukten verwendete Kontrollwerkstoffe hervorgerufenen Gewebsreaktion beurteilt, deren klinische Vertretbarkeit und deren Merkmale der Bioverträglichkeit festgestellt worden sind. Das Ziel der Prüfverfahren ist die Charakterisierung der Vorgeschichte und des Verlaufs der Gewebsreaktion nach Implantation eines Medizinproduktes bzw. Biomaterials, einschließlich der endgültigen Aufnahme oder der Resorption bzw. des Abbaus des Werkstoffs. Insbesondere bei abbaufähigen bzw. resorbierbaren Werkstoffen sollten die Abbaumerkmale des Werkstoffs und die sich daraus ergebende Gewebsreaktion ermittelt werden.
Dieser Teil von ISO 10993 behandelt nicht die systemische Toxizität, die Karzinogenität, die Teratogenität oder die Mutagenität.

Évaluation biologique des dispositifs médicaux - Partie 6: Essais concernant les effets locaux après implantation (ISO 10993-6:2007)

Biološko ovrednotenje medicinskih pripomočkov - 6. del: Preskusi, povezani z lokalnimi učinki po implantaciji (ISO 10993-6:2007)

General Information

• Status: Withdrawn
• Publication Date: 14-Apr-2007
• Withdrawal Date: 19-May-2009
• 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: 9960 - Withdrawal effective - Withdrawal
• Start Date: 20-May-2009
• Completion Date: 20-May-2009
• Directive: 90/385/EEC - Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning 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 10993-6:2007 - Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6:2007)

Relations

• Replaces: EN 30993-6:1994 - Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6:1994)
• Effective Date: 22-Dec-2008
• Replaced By: EN ISO 10993-6:2009 - Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6:2007)
• Effective Date: 30-May-2009

Standards Content (Sample)

SLOVENSKI STANDARD
01-september-2007
1DGRPHãþD
SIST EN 30993-6:2000
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO3UHVNXVLSRYH]DQL]
ORNDOQLPLXþLQNLSRLPSODQWDFLML,62
Biological evaluation of medical devices - Part 6: Tests for local effects after implantation
(ISO 10993-6:2007)
Biologische Beurteilung von Medizinprodukten - Teil 6: Prüfungen auf lokale Effekte nach
Implantationen (ISO 10993-6:2007)
Évaluation biologique des dispositifs médicaux - Partie 6: Essais concernant les effets
locaux apres implantation (ISO 10993-6:2007)
Ta slovenski standard je istoveten z: EN ISO 10993-6:2007
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 10993-6
NORME EUROPÉENNE
EUROPÄISCHE NORM
April 2007
ICS 11.100.20 Supersedes EN 30993-6:1994
English Version
Biological evaluation of medical devices - Part 6: Tests for local
effects after implantation (ISO 10993-6:2007)
Évaluation biologique des dispositifs médicaux - Partie 6: Biologische Beurteilung von Medizinprodukten - Teil 6:
Essais concernant les effets locaux après implantation Prüfungen auf lokale Effekte nach Implantationen (ISO
(ISO 10993-6:2007) 10993-6:2007)
This European Standard was approved by CEN on 13 March 2007.
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: rue de Stassart, 36  B-1050 Brussels
© 2007 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-6:2007: E
worldwide for CEN national Members.

Foreword
This document (EN ISO 10993-6:2007) has been prepared by Technical Committee ISO/TC 194
"Biological evaluation of medical devices" in collaboration with Technical Committee CEN/TC 206
"Biocompatibility of medical and dental materials and 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 2007, and conflicting national standards shall
be withdrawn at the latest by October 2007.

This document supersedes EN 30993-6:1994.

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(s).

For relationship with EU Directive(s), 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 United Kingdom.

Endorsement notice
The text of ISO 10993-6:2007 has been approved by CEN as EN ISO 10993-6:2007 without any
modifications.
Annex ZA
(informative)
Clauses of this International Standard addressing essential requirements
or other provisions of EU Directives 90/385/EEC for Active Implantable
Medical Devices and 93/42/EEC for Medical Devices

This International Standard 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
Directives 90/385/EEC for Active Implantable Medical Devices and 93/42/EEC for 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 the Directives and
associated EFTA regulations.
Table ZA 1— Correspondence between this International Standard and Directives 90/385/EEC
and 93/42/EEC
Clause(s)/Sub-clause(s) of Essential requirements (ERs) of Qualifying remarks/Notes
this International Standard Directive 90/385/EEC and 93/42/EEC
4,5,6 & Annexes B, C, D 9 of Annex I of 90/385/EEC The test methods do not include
pass/fail criteria
7.1 of Annex I of 93/42/EEC
WARNING: Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this International Standard.

INTERNATIONAL ISO
STANDARD 10993-6
Second edition
2007-04-15
Biological evaluation of medical
devices —
Part 6:
Tests for local effects after implantation
Évaluation biologique des dispositifs médicaux —
Partie 6: Essais concernant les effets locaux après implantation

Reference number
ISO 10993-6:2007(E)
©
ISO 2007
ISO 10993-6:2007(E)
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ii © ISO 2007 – All rights reserved

ISO 10993-6:2007(E)
Contents Page
Foreword. iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions. 2
4 Common provisions for implantation test methods . 2
4.1 General. 2
4.2 Preparation of specimens for implantation .2
5 Test methods, general aspects . 3
5.1 Tissue and implantation site . 3
5.2 Animals . 3
5.3 Test periods. 4
5.4 Surgery and testing conditions. 5
5.5 Evaluation. 6
6 Test report . 8
Annex A (informative) General considerations regarding implantation periods and tissue
responses to degradable/resorbable materials. 9
Annex B (normative) Test methods for implantation in subcutaneous tissue . 10
Annex C (normative) Test method for implantation in muscle. 12
Annex D (normative) Test method for implantation in bone . 14
Annex E (informative) Examples of evaluation of local biological effects after implantation. 17
Bibliography . 19

ISO 10993-6:2007(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 10993-6 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This second edition cancels and replaces the first edition (ISO 10993-6:1994) which has been technically
revised.
ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:
⎯ Part 1: Evaluation and testing within a risk management system
⎯ 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 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
iv © ISO 2007 – All rights reserved

ISO 10993-6:2007(E)
⎯ Part 16: Toxicokinetic study design for degradation products and leachables
⎯ Part 17: Establishment of allowable limits for leachable substances
⎯ Part 18: Chemical characterization of materials
⎯ Part 19: Physico-chemical, morphological and topographical characterization of materials
⎯ Part 20: Principles and methods for immunotoxicology testing of medical devices
For the purposes of this part of ISO 10993 the CEN annex regarding fulfilment of European Council Directives
will be removed at publication stage.
INTERNATIONAL STANDARD ISO 10993-6:2007(E)

Biological evaluation of medical devices —
Part 6:
Tests for local effects after implantation
1 Scope
This part of ISO 10993 specifies test methods for the assessment of the local effects after implantation of
biomaterials intended for use in medical devices.
This part of ISO 10993 applies to materials that are:
⎯ solid and non-biodegradable;
⎯ degradable and/or resorbable;
⎯ non-solid, such as porous materials, liquids, pastes and particulates.
The test specimen is impl
...