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: 9599 - Withdrawal of International Standard
• Start Date: 30-May-2025
• Completion Date: 13-Dec-2025

Relations

• Revised: ISO/TS 20721:2025 - Implants for surgery - Absorbable implants - General guidelines and requirements for assessment of absorbable metallic implants
• Effective Date: 08-Jul-2024

Overview

ISO/TS 20721:2020, "Implants for surgery - General guidelines and requirements for assessment of absorbable metallic implants," provides guidance on evaluating metals and implants that are designed to be fully absorbed by the host. The Technical Specification clarifies how testing and assessment differ from procedures for permanent, non‑absorbable metallic implants and focuses on materials considerations, in vitro degradation/fatigue characterization, and biological evaluation to reduce misleading or erroneous test results.

Key Topics and Requirements

• Scope and purpose: Guidance for assessment of implants fabricated wholly or partly from absorbable metals; not applicable to non‑absorbable or non‑metallic components (e.g., polymeric coatings, pharmaceuticals).
• Absorbable metal types: Describes common base elements (magnesium, iron, zinc) and the role of alloying elements in performance and degradation behavior.
• Design considerations: Composition, coatings, non‑absorbable subcomponents, microstructure and implant geometry influence absorption and mechanical performance over time.
• Absorption and degradation: Outlines the absorption process, metallic conversion, subsequent degradation reactions, elemental impact, biological absorption, and mechanical loss during corrosion.
• Metallurgical and manufacturing factors: Highlights raw material purity, melting/casting/thermo‑mechanical processing, surface condition, and packaging/sterilization impacts on performance.
• In vitro degradation and fatigue: Emphasizes environmental conditions and test design that reflect physiological realities to avoid misleading corrosion/fatigue results.
• Biological evaluation: Covers biocompatibility of degradation products, in vitro biological testing, and in vivo studies including biocompatibility end points and animal safety/performance testing.
• Complementary guidance: Intended to complement-not replace-existing device‑ and application‑specific standards; consult implant‑specific standards where applicable.

Applications

ISO/TS 20721:2020 is practical for:

• Designing and qualifying absorbable metallic implants such as fixation devices and other temporary implants used in surgical applications.
• Developing test protocols for in vitro degradation, fatigue testing, and biological evaluation that account for absorbable‑specific behavior.
• Informing risk assessments about degradation products, systemic exposure, and mechanical integrity during absorption.

Who Should Use This Standard

• Implant manufacturers developing absorbable metal devices
• Material suppliers providing absorbable alloys or coatings
• Test laboratories performing corrosion, fatigue, and biocompatibility testing
• Regulatory and quality professionals assessing preclinical data and conformity
• R&D teams working on alloy design and processing for medical implants

Related Standards

• ISO/TS 37137‑1 (Biological evaluation guidance for absorbable implants)
• ISO/TR 37137‑2 (specific to magnesium‑based absorbable materials; under development)
• ASTM F3160 (metallurgical characterization of absorbable metallic materials)
• ASTM F3268 (in vitro degradation testing of absorbable metals)
• ISO 10993 series (biological evaluation of medical devices)

Keywords: ISO/TS 20721:2020, absorbable metallic implants, absorbable metals, in vitro degradation, biological evaluation, metallurgical considerations, implant testing, medical device standards.

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
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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
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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).
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constitute an endorsement.
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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 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.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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.
3)
ISO/TS 37137-1, Biological evaluation of medical devices — Part 1: Guidance for absorbable implants
ASTM F3160, Standard guide for metallurgical characterization of absorbable metallic materials for
surgical implants
ASTM F3268, Standard guide for in vitro degradation testing of absorbable metals
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3) Under preparation. Stage at the time of publication: ISO/TS/CD 37137-1:2020.
3.1
absorb
absorption
action of a non-endogenous (foreign) material or substance, or its decomposition
products passing through or being assimilated by cells and/or tissue over time
Note 1 to entry: Annex A provides further clarification regarding the nomenclature of absorb, degrade and
related terms.
[SOURCE: ISO 10993-6:2016, 3.1, modified — Note 1 to entry added.]
3.2
degrade
physically, metabolically, and/or chemically decompose a material or substance
[SOURCE: ISO/TS 37137-1:2020, 3.4]
3.3
degradation product
byproduct
intermediate or final result from the physical, metabolic, and/or chemical decomposition of a material
or substance
[SOURCE: ISO/TS 37137-1:2020, 3.3]
3.4
implant
implantable medical device
medical device which can only be removed by medical or surgical intervention and which is intended to:
— be totally or partially introduced into the human body or a natural orifice, or
— replace an epithelial surface or the surface of the eye, and
— remain after the procedure for at least 30 days
[SOURCE: ISO 13485:2016, 3.6, modified — alternative term “implant” added.]
4 Absorbable metal considerations
4.1 General
Implants fabricated from absorbable metals are expected to degrade gradually while retaining sufficient
mechanical properties over time to achieve a clinically successful end point. As these implants degrade
by corrosion, their degradation products should be released at a rate which is acceptable to the host
both locally and systemically. Generally, absorbable metals are primarily composed of one of three main
nutrient elements: magnesium, iron, or zinc. Various alloying elements are commonly added to each
of these base materials to improve properties like strength, ductility, fatigue resistance, or corrosion
resistance. In some cases, non-metallic coatings or components can be added to the absorbable metal to
augment the total implant performance.
In contrast, non-absorbable metallic implants (or subcomponents) intended to permanently replace
a missing, lacking, destroyed, or diseased physiological function, or to support healing process are
intentionally resistant to corrosion. Since the corrosion rate of such implants is extremely slow to
negligible, such alloys can include toxic or harmful elements which are not expected to significantly
leach into the body but rather remain within the implant. In some cases (e.g. metal on metal hip
implants), wear particles of these corrosion-resistant alloys can be generated and can lead to negative
outcomes due to their non-absorbing nature. Since most current standards have been developed with
such permanent implants in mind, these standards need to be carefully evaluated for their suitability
as test methods for absorbable metals.
2 © ISO 2020 – All rights reserved

4.2 Design considerations
4.2.1 Composition
4.2.1.1 General
All components of the absorbable metal are intended to be directly or indirectly exposed to the body
tissue where the potential for an adverse biological response can occur. Informed decisions shall
be made on the toxicity profile of the materials including potential impurities and their resultant
degradation products. As the implants progress through the corrosion process, they produce a series of
degradation products including ions, oxides, hydroxides and gases (see Reference Zheng 2014). Further,
metallic particles can be released from the implant during the corrosion process which can result
in transient mechanical and biological impacts in addition to the degradation products mentioned
previously.
Components of the absorbable metal native to the host, such as magnesium, iron, or zinc, can simply be
incorporated in the body’s various biological processes, with excesses removed by natural homeostasis
mechanisms. However, in some physiological circumstances, the components and degradation products
can have long residence periods in either the initial implant site or a remote tissue after transport.
A general understanding of what happens to the implant’s resulting degradation products during its
absorption lifecycle is important.
4.2.1.2 Base element
It is recommended to use metals considered native to the body, examples of which are iron, magnesium,
or zinc.
Assessment for biocompatibility of the base element shall be done according to 7.2.
4.2.1.3 Alloying elements
Alloying elements are intentionally added to the base element to improve properties like tensile
strength or corrosion rate. These elements can account for a significant portion of the alloy, and thus
require a high level of scrutiny. Unlike the base elements which are easily removed by the body, the
alloying elements are often not nutrient metals, and can sometimes have longer residence times in the
implant-site tissue. They can also be transported by the body to other tissues for further processing.
It is important to consider the degradation pathways, residence locations and residence durations of
these alloying elements.
Assessment for biocompatibility of the alloying elements and their compounds (metal phases and
intermetallic compounds) shall be done according to 7.2.
4.2.1.4 Impurities
Impurities are those elements that are not purposely added to the alloy but are introduced through
raw material impurities and/or processing. Within this context, impurities include, but are not limited
to, trace elements, contaminant materials, and unintended elements. Impurities should normally be
present at very low concentrations. The primary concern with impurities is their impact on implant
performance and safety. In the case of magnesium alloys, for example, trace iron, nickel, or copper
can dramatically reduce corrosion resistance by forming microgalvanic cells between the anodic
magnesium and cathodic impurity. In all metals, inclusions (e.g. oxides, nitrides, intermetallics)
exceeding some critical size can also limit implant strength and fatigue life. Proper risk and quality
management systems should ensure these impurities are sufficiently low to avoid these negative side
effects.
ASTM B107/B107M, ASTM B93/B93M, ASTM B90/B90M, and the ASM Specialty Handbook for Magnesium
and Magnesium Alloys contain useful information on impurity limits in common magnesium alloys.
ASTM A36 and ASTM A314 detail impurity limits for some commercially available iron-based materials.
ASTM B86 sets impurity limits for commercially available zinc alloys.
NOTE ASTM B107/B107M, ASTM B93/B93M, ASTM B90/B90M, ASTM A36, ASTM A314, ASTM B86, and ASM
Specialty Handbook for Magnesium and Magnesium Alloys cited here are for information only.
4.2.2 Coatings
In some implants, a coating can be initially employed to alter the corrosion behaviour (including the
corrosion rate, corrosion uniformity, corrosion mechanisms, and corrosion products) and failure
modes. Coatings can take the form of a conversion layer (oxides/passivation) or extraneous materials
(e.g. polymers, metals, or ceramics). When designing in vitro and in vivo tests, it is important to consider
and evaluate the impact of any coatings intentionally applied to the implant. Potential interactions
between the coating, absorbable metal substrate, and degradation products from the coating and/or
the absorbable metal substrate should be considered.
4.2.3 Non-absorbable subcomponents
Some subcomponents of absorbable metals can be designed to remain permanently in the body. For
example, small tantalum or platinum markers can be added to a vascular scaffold to increase radiopacity
and aid in deployment.
4.2.4 Microstructure
The microstructure of an absorbable metal can have a significant impact on nearly all aspects of
mechanical performance. It can also impact corrosion behaviour which can impact biological response.
Mechanical properties like strength, toughness, and ductility, as well as corrosion rate and corrosion
morphology, are strongly tied to the metal’s microstructure. In the case of additively manufactured
components, understanding porosity can be important as well. Amorphous metals, also known as
metallic glasses, do not have the typical crystalline structure found in most metals and requires special
consideration. At micro and nano scales, there are five major factors that impact the performance of the
material:
a) the size and distribution of grains and subgrains (individual crystallites in metals);
b) crystallographic texture (orientation of grains);
c) presence, type, morphology, size, volume fraction, orientation relative to the matrix/ coherency,
chemical composition, structure, and distribution of intermetallic phases, inclusions, or pores;
d) concentration of solute atoms within the phases (matrix phase and intermetallic phases);
e) concentration and distribution of defects (e.g. dislocations, vacancies, interstitials) within the
crystal structure.
A metal’s microstructure is a function of both its chemistry (base and alloying elements) and its
processing history. Therefore, metallic materials with equivalent chemistries but different process
histories possess different microstructures. Likewise, metals with identical process history but
different chemistries also have different microstructures. Further discussion on processing can be
found in 5.3.
Because a consistent microstructure can be critical to an implant’s performance, inspection for
appropriate retention of the microstructure should be undertaken at appropriate stages in the
manufacturing process. ASTM F3160 provides significant information and guidance regarding the
metallurgical (and microstructural) characterization of magnesium (Mg), iron (Fe), and zinc (Zn)
based metals and alloys. Generally, metallic microstructures are observed by optical (light) or electron
microscopy.
NOTE ASTM E407, ASTM E340, ASTM E112, ASTM E1382, ASTM E2627 and ISO 643 provide methods for
sample preparation and characterization of the microstructure.
4 © ISO 2020 – All rights reserved

4.2.5 Implant design and functional performance
The absorbable implantable medical implant shall accomplish its intended clinical treatment over
a sufficient time period to provide a clinically successful outcome. The implant shall be designed to
be absorbed by the body over a finite time and eliminated such that there is no residual complication
by the former presence of the implant or significant persistent residuals. The implant shall meet the
performance requirements expected for the clinical treatment and maintain sufficient integrity during
the tissue healing and remodeling period to not adversely affect the implant site. Additionally, the
components of the alloy, their degradation products and intermediates shall result in an acceptable
biological response, and the risks associated with local pH changes, gas bubble formation, heat
generation, and adverse responses to changes in mechanical properties with degradation shall also be
assessed – see 4.2.1, 4.3.5, and Clause 7.
The implant performance at the time of implantation shall meet the applicable requirements. Legal
requirements can apply, that define specific implant performance for the implant type. An appropriate
level of performance shall be maintained during the healing process as required by the treatment.
The degree of performance required at any time point s
...