ISO/TS 20721:2025

Technical
Specification
ISO/TS 20721
Second edition
Implants for surgery — Absorbable
2025-05
implants — General guidelines and
requirements for assessment of
absorbable metallic implants
Implants chirurgicaux — Implants absorbables — Lignes
directrices et exigences générales pour l'évaluation des implants
métalliques absorbables
Reference number
© ISO 2025
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ii
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 .4
4.3 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 . 7
5.1 General .7
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

iii
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
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This document was prepared by Technical Committee ISO/TC 150, Implants for surgery.
This second edition cancels and replaces the first edition (ISO/TS 20721:2020), which has been technically
revised.
The main change is as follows: references have been updated.
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
Introduction
This document provides general information regarding implantable absorbable metals, a detailed description
of their absorption processes and an outline of the design considerations which differ significantly from
non-absorbable metals.
This document discusses:
— the metallurgical evaluation of absorbable metals with reference to ASTM F3160, with a commentary on
the impact of composition and production processes on the final performance;
— in vitro degradation corrosion testing with reference to ASTM F3268, with a commentary on the
importance of environmental conditions in the tests;
— in vitro and in vivo biological assessments, with reference to several parts of the ISO 10993 series and
ISO/TS 37137-1.
NOTE ISO/TS 37137-1 applies to all absorbable materials, including metals and polymers.
The interrelation of this document with various absorbable-specific reference documents is shown in
Figure 1.
Figure 1 — Interrelation of this document with standards specific to absorbable metallic implants
This document 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-
[23]
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.

v
Technical Specification ISO/TS 20721:2025(en)
Implants for surgery — Absorbable implants — General
guidelines and requirements for assessment of absorbable
metallic implants
1 Scope
This document establishes 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.
ISO/TS 37137-1, Biological evaluation of absorbable medical devices — Part 1: General requirements
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 terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/

3.1
absorb
absorption, noun
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 (3.2) and
related terms.
[SOURCE: ISO 10993-6:2016, 3.1, modified — the domain and Note 1 to entry have been added.]
3.2
degrade
physically, metabolically and/or chemically decompose a material or substance
[SOURCE: ISO/TS 37137-1:2021, 3.3]
3.3
degradation product
intermediate or final result from the physical, metabolic and/or chemical decomposition of a material or
substance
[SOURCE: ISO/TS 37137-1:2021, 3.2, modified — "agent" has been replaced with "substance".]
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 — “implant” has been added as the preferred term and Note 1 to
entry has been deleted.]
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.

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 [26]). 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 life
cycle 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, zinc
or molybdenum.
The assessment for biocompatibility of the base element shall be done in accordance with 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.
The assessment for biocompatibility of the alloying elements and their compounds (metal phases and
intermetallic compounds) shall be done in accordance with 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.
[13] [14] [15]
ASTM B107/B107M , ASTM B93/B93M , ASTM B90/B90M and the ASM Specialty Handbook
[25]
for Magnesium and Magnesium Alloys contain useful information on impurity limits in common
magnesium alloys.
[9] [10]
ASTM A36 and ASTM A314 contain useful information on impurity limits for some commercially
available iron-based materials.

[12]
ASTM B86 contains useful information on impurity limits for commercially available zinc alloys.
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, the
absorbable metal substrate, and the 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) the 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.
Given that 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.
[19] [18] [17] [21] [22]
NOTE ASTM E407 , ASTM E340 , ASTM E112 , ASTM E1382 , ASTM E2627 and ISO 643 provide
methods for sample preparation and characterization of the microstructure.
4.2.5 Implant design and functional performance
The absorbable metallic 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 remode
...