EN ISO 10993-11:2006

Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11:2006)

This part of ISO 10993 specifies methodologies for the evaluation of the systematic toxicity potential of medical devices with release constituents into the body. In addition, it includes pyrogenicity testing.  The test methods cited in this part of ISO 10993 are from International Standards, national standards, directives and regulations. This part of ISO 10993 is concerned with either the actual product or its leachables. It is intended that tests for extracts or leachables be conducted by choosing appropriate extraction vehicles to yield a maximum  extraction of leachable materials, in order to conduct biological testing.

Biologische Beurteilung von Medizinprodukten - Teil 11: Prüfungen auf systemische Toxizität (ISO 10993-11:2006)

Dieser Teil von ISO 10993 legt Anforderungen an Verfahren fest und gibt eine Anleitung, die bei der Beurteilung des Potenzials von Materialien für Medizinprodukte zur Auslösung nachteiliger systemischer Re¬aktionen zu befolgen sind.

Évaluation biologique des dispositifs médicaux - Partie 11: Essais de toxicité systémique (ISO 10993-11:2006)

Biološko ovrednotenje medicinskih pripomočkov – 11. del: Preskusi sistemske toksičnosti (ISO 10993-11:2006)

General Information

• Status: Withdrawn
• Publication Date: 14-Aug-2006
• Withdrawal Date: 28-Apr-2009
• ICS: 11.100 - Laboratory medicine
• 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: 29-Apr-2009
• Completion Date: 29-Apr-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 10993-11:2006 - Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11:2006)

Relations

• Replaces: EN ISO 10993-11:1995 - Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11:1993)
• Effective Date: 22-Dec-2008
• Replaced By: EN ISO 10993-11:2009 - Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11:2006)
• Effective Date: 22-Dec-2008

Standards Content (Sample)

SLOVENSKI STANDARD
01-oktober-2006
1DGRPHãþD
SIST EN ISO 10993-11:2000
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRY±GHO3UHVNXVLVLVWHPVNH
WRNVLþQRVWL,62
Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-
11:2006)
Biologische Beurteilung von Medizinprodukten - Teil 11: Prüfungen auf systemische
Toxizität (ISO 10993-11:2006)
Évaluation biologique des dispositifs médicaux - Partie 11: Essais de toxicité systémique
(ISO 10993-11:2006)
Ta slovenski standard je istoveten z: EN ISO 10993-11:2006
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 10993-11
NORME EUROPÉENNE
EUROPÄISCHE NORM
August 2006
ICS 11.100.20 Supersedes EN ISO 10993-11:1995
English Version
Biological evaluation of medical devices - Part 11: Tests for
systemic toxicity (ISO 10993-11:2006)
Évaluation biologique des dispositifs médicaux - Partie 11: Biologische Beurteilung von Medizinprodukten - Teil 11:
Essais de toxicité systémique (ISO 10993-11:2006) Prüfungen auf systemische Toxizität (ISO 10993-11:2006)
This European Standard was approved by CEN on 7 August 2006.

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, 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
© 2006 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-11:2006: E
worldwide for CEN national Members.

Foreword
This document (EN ISO 10993-11:2006) 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 February 2007, and conflicting national standards
shall be withdrawn at the latest by February 2007.

This document supersedes EN ISO 10993-11:1995.

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, 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 10993-11:2006 has been approved by CEN as EN ISO 10993-11:2006 without any
modifications.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directives 90/385/EEC and 93/42/EEC

This European Standard has been prepared under a mandate given to CEN by the European
Commission to provide one means of conforming to Essential Requirements of the New Approach
Directives 90/385/EEC and 93/42/EEC.
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
normative clauses of this standard confers, within the limits of the scope of this standard, a
presumption of conformity with the relevant Essential Requirements of that Directive and associated
EFTA regulations.
WARNING: Other requirements and other EU Directives may be applicable to the products falling
within the scope of this standard.

INTERNATIONAL ISO
STANDARD 10993-11
Second edition
2006-08-15
Biological evaluation of medical
devices —
Part 11:
Tests for systemic toxicity
Évaluation biologique des dispositifs médicaux —
Partie 11: Essais de toxicité systémique

Reference number
ISO 10993-11:2006(E)
©
ISO 2006
ISO 10993-11:2006(E)
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ISO 10993-11:2006(E)
Contents Page
Foreword. iv
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions. 1
4 General considerations. 2
4.1 General. 2
4.2 Selection of animal species. 3
4.3 Animal status . 3
4.4 Animal care and husbandry. 3
4.5 Size and number of groups . 3
4.6 Route of exposure . 4
4.7 Sample preparation . 4
4.8 Dosing. 5
4.9 Body weight and food/water consumption . 6
4.10 Clinical observations. 6
4.11 Clinical pathology. 6
4.12 Anatomic pathology . 7
4.13 Study designs . 7
4.14 Quality of investigation . 7
5 Acute systemic toxicity. 7
5.1 General. 7
5.2 Study design . 8
5.3 Evaluation criteria. 9
5.4 Final report . 10
6 Repeated exposure systemic toxicity (subacute, subchronic and chronic systemic
toxicity) . 11
6.1 General. 11
6.2 Study design . 12
6.3 Evaluation criteria. 14
6.4 Final report . 15
Annex A (informative) Routes of administration. 16
Annex B (informative) Dosage volumes. 18
Annex C (informative) Common clinical signs and observations. 19
Annex D (informative) Suggested haematology, clinical chemistry and urinalysis measurements . 20
Annex E (informative) Suggested organ list for histopathological evaluation . 22
Annex F (informative) Information on material-mediated pyrogens . 24
Bibliography . 26

ISO 10993-11:2006(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 10993-11 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.
This second edition cancels and replaces the first edition (ISO 10993-11:1993) 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
⎯ 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: Te
...