ISO/TS 20721:2020

Implants for surgery — General guidelines and requirements for assessment of absorbable metallic implants

This document established the currently recognized approaches and special considerations needed when evaluating the in vitro and in vivo performance of absorbable metals and implants fabricated, in whole or in part, from them. This document describes how the evaluation of these metals can differ from those utilized for permanent non-absorbable implantable implants (or subcomponents), in that absorbable metal implants (or subcomponents) are — by design — intended to be absorbed in their entirety by the host. This document provides guidance regarding the materials considerations, in vitro degradation/fatigue characterization, and biological evaluation of medical implants made of absorbable metals. The provided content is intended to deliver added clarity to the evaluation of these materials and implants to increase awareness of critical factors and reduce potential for generation of erroneous or misleading test results. While this document and the herein described referenced standards contain many suggested alterations or modifications to currently practiced procedures or specifications, the provided content is intended to complement, and not replace, current conventions regarding the assessment of implantable implants. This document covers the evaluation of absorbable metal specific attributes in general and is not intended to cover application or implant specific considerations. Thus, it is important to consult relevant implant and/or application specific standards. This document does not apply to non-absorbable or non-metallic components (e.g. polymeric coatings, pharmaceuticals, non-absorbable metals) used in conjunction with absorbable metal implants.

Implants chirurgicaux — Lignes directrices et exigences générales pour l'évaluation des implants métalliques absorbables

General Information

• Status: Published
• Publication Date: 14-Sep-2020
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: ISO/TC 150 - Implants for surgery
• Drafting Committee: ISO/TC 150 - Implants for surgery
• Current Stage: 9092 - International Standard to be revised
• Completion Date: 28-Mar-2024

Standards Content (Sample)

TECHNICAL ISO/TS
SPECIFICATION 20721
First edition
2020-09
Implants for surgery — General
guidelines and requirements for
assessment of absorbable metallic
implants
Reference number
©
ISO 2020
© 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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Absorbable metal considerations . 2
4.1 General . 2
4.2 Design considerations. 3
4.2.1 Composition . 3
4.2.2 Coatings . 4
4.2.3 Non-absorbable subcomponents . 4
4.2.4 Microstructure . 4
4.2.5 Implant design and functional performance . 5
4.3 The absorption process . 5
4.3.1 General outline . 5
4.3.2 Metallic conversion . 5
4.3.3 Subsequent degradation reactions . 6
4.3.4 Elemental impact on absorption . 6
4.3.5 Biological absorption . 6
4.3.6 Mechanical loss . 6
5 Metallurgical and manufacturing considerations . 8
5.1 General . 8
5.2 Composition . 8
5.3 Production process . . 8
5.3.1 General. 8
5.3.2 Raw material purity . 8
5.3.3 Metal melting practice . 8
5.3.4 Metal casting. 8
5.3.5 Metal thermo-mechanical processing . 8
5.3.6 Surface considerations . 9
5.3.7 Implant cleaning, sterilization, packaging, storage, and handling . 9
6 Evaluation of in vitro degradation characteristics . 9
6.1 General . 9
6.2 Additional considerations . 9
7 Biological evaluation .10
7.1 General .10
7.2 Biocompatibility of degradation products .10
7.3 In vitro biological evaluation .10
7.4 In vivo biological evaluation .10
7.4.1 Biocompatibility end point studies .10
7.4.2 Animal safety and implant performance studies .11
Annex A (informative) Nomenclature of absorb, degrade and related terms .12
Bibliography .13
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 150, Implants for surgery.
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

Introduction
This document provides a general introduction to the field of absorbable metals. It outlines design
considerations which differ from non-absorbable metals and provides a detailed description of the
absorption process.
Metallurgical evaluation of absorbable metals is discussed, with reference to ASTM F3160 and
commentary on the impact of composition and production processes on final performance.
In vitro degradation corrosion testing is discussed, with reference to ASTM F3268 and commentary on
the importance of environmental conditions in the tests.
Both in vitro and in vivo biological assessment are discussed, with reference to several parts of the
1) 2)
ISO 10993 series, ISO/TS 37137-1 and the under-development ISO/TR 37137-2 .
NOTE ISO/TS 37137-1 applies to all absorbable materials, including metals and polymers. ISO/TR 37137-2 is
specific to absorbable magnesium-based materials.
The interrelation of the absorbable-specific reference documents can be viewed in Figure 1.
Figure 1 — Interrelation of standards specific to absorbable implants
The guide can be useful to both material suppliers and implant manufacturers.
Absorbable polymers used in conjunction with absorbable metals, either for performance modification
or drug delivery, are not addressed. However, it is expected that a polymer coating, absorbable or non-
absorbable, can influence absorption and performance of the underlying absorbable metal. ASTM F2902
addresses absorbable polymers.
Some existing standards address specific absorbable implants (e.g. ISO/TS 17137 addresses absorbable
cardiovascular implants) made of either polymer or metal.
1) Under preparation. Stage at the time of publication: ISO/TS/CD 37137-1:2020.
2) Under preparation. Stage at the time of publication: ISO/TS/CD 37137-2:2020.
TECHNICAL SPECIFICATION ISO/TS 20721:2020(E)
Implants for surgery — General guidelines and
requirements for assessment of absorbable metallic
implants
1 Scope
This document established the currently recognized approaches and special considerations needed
when evaluating the in vitro and in vivo performance of absorbable metals and implants fabricated, in
whole or in part, from them. This document describes how the evaluation of these metals can differ
from those utilized for permanent non-absorbable implantable implants (or subcomponents), in that
absorbable metal implants (or subcomponents) are — by design — intended to be absorbed in their
entirety by the host.
This document provides guidance regarding the materials considerations, in vitro degradation/
fatigue characterization, and biological evaluation of medical implants made of absorbable metals. The
provided content is intended to deliver added clarity to the evaluation of these materials and implants
to increase awareness of critical factors and reduce potential for generation of erroneous or misleading
test results.
While this document and the herein described referenced standards contain many suggested alterations
or modifications to currently practiced procedures or specifications, the provided content is intended
to complement, and not replace, current conventions regarding the assessment of implantable implants.
This document covers the evaluation of absorbable metal specific attributes in general and is not
intended to cover application or implant specific considerations. Thus, it is important to consult relevan
...

TECHNICAL ISO/TS
SPECIFICATION 20721
First edition
2020-09
Implants for surgery — General
guidelines and requirements for
assessment of absorbable metallic
implants
Reference number
©
ISO 2020
© 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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Absorbable metal considerations . 2
4.1 General . 2
4.2 Design considerations. 3
4.2.1 Composition . 3
4.2.2 Coatings . 4
4.2.3 Non-absorbable subcomponents . 4
4.2.4 Microstructure . 4
4.2.5 Implant design and functional performance . 5
4.3 The absorption process . 5
4.3.1 General outline . 5
4.3.2 Metallic conversion . 5
4.3.3 Subsequent degradation reactions . 6
4.3.4 Elemental impact on absorption . 6
4.3.5 Biological absorption . 6
4.3.6 Mechanical loss . 6
5 Metallurgical and manufacturing considerations . 8
5.1 General . 8
5.2 Composition . 8
5.3 Production process . . 8
5.3.1 General. 8
5.3.2 Raw material purity . 8
5.3.3 Metal melting practice . 8
5.3.4 Metal casting. 8
5.3.5 Metal thermo-mechanical processing . 8
5.3.6 Surface considerations . 9
5.3.7 Implant cleaning, sterilization, packaging, storage, and handling . 9
6 Evaluation of in vitro degradation characteristics . 9
6.1 General . 9
6.2 Additional considerations . 9
7 Biological evaluation .10
7.1 General .10
7.2 Biocompatibility of degradation products .10
7.3 In vitro biological evaluation .10
7.4 In vivo biological evaluation .10
7.4.1 Biocompatibility end point studies .10
7.4.2 Animal safety and implant performance studies .11
Annex A (informative) Nomenclature of absorb, degrade and related terms .12
Bibliography .13
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 150, Implants for surgery.
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

Introduction
This document provides a general introduction to the field of absorbable metals. It outlines design
considerations which differ from non-absorbable metals and provides a detailed description of the
absorption process.
Metallurgical evaluation of absorbable metals is discussed, with reference to ASTM F3160 and
commentary on the impact of composition and production processes on final performance.
In vitro degradation corrosion testing is discussed, with reference to ASTM F3268 and commentary on
the importance of environmental conditions in the tests.
Both in vitro and in vivo biological assessment are discussed, with reference to several parts of the
1) 2)
ISO 10993 series, ISO/TS 37137-1 and the under-development ISO/TR 37137-2 .
NOTE ISO/TS 37137-1 applies to all absorbable materials, including metals and polymers. ISO/TR 37137-2 is
specific to absorbable magnesium-based materials.
The interrelation of the absorbable-specific reference documents can be viewed in Figure 1.
Figure 1 — Interrelation of standards specific to absorbable implants
The guide can be useful to both material suppliers and implant manufacturers.
Absorbable polymers used in conjunction with absorbable metals, either for performance modification
or drug delivery, are not addressed. However, it is expected that a polymer coating, absorbable or non-
absorbable, can influence absorption and performance of the underlying absorbable metal. ASTM F2902
addresses absorbable polymers.
Some existing standards address specific absorbable implants (e.g. ISO/TS 17137 addresses absorbable
cardiovascular implants) made of either polymer or metal.
1) Under preparation. Stage at the time of publication: ISO/TS/CD 37137-1:2020.
2) Under preparation. Stage at the time of publication: ISO/TS/CD 37137-2:2020.
TECHNICAL SPECIFICATION ISO/TS 20721:2020(E)
Implants for surgery — General guidelines and
requirements for assessment of absorbable metallic
implants
1 Scope
This document established the currently recognized approaches and special considerations needed
when evaluating the in vitro and in vivo performance of absorbable metals and implants fabricated, in
whole or in part, from them. This document describes how the evaluation of these metals can differ
from those utilized for permanent non-absorbable implantable implants (or subcomponents), in that
absorbable metal implants (or subcomponents) are — by design — intended to be absorbed in their
entirety by the host.
This document provides guidance regarding the materials considerations, in vitro degradation/
fatigue characterization, and biological evaluation of medical implants made of absorbable metals. The
provided content is intended to deliver added clarity to the evaluation of these materials and implants
to increase awareness of critical factors and reduce potential for generation of erroneous or misleading
test results.
While this document and the herein described referenced standards contain many suggested alterations
or modifications to currently practiced procedures or specifications, the provided content is intended
to complement, and not replace, current conventions regarding the assessment of implantable implants.
This document covers the evaluation of absorbable metal specific attributes in general and is not
intended to cover application or implant specific considerations. Thus, it is important to consult relevan
...