ISO/TS 37137-1:2021
(Main)Biological evaluation of absorbable medical devices — Part 1: General requirements
Biological evaluation of absorbable medical devices — Part 1: General requirements
This document specifies the requirements for the evaluation of absorbable medical devices during a biological risk assessment based on ISO 10993-1, including a clarification of the terms "absorb", "degrade" and other related terms (see Annex A).
Évaluation biologique des dispositifs médicaux résorbables — Partie 1: Exigences générales
General Information
Buy Standard
Standards Content (Sample)
TECHNICAL ISO/TS
SPECIFICATION 37137-1
First edition
2021-03
Biological evaluation of absorbable
medical devices —
Part 1:
General requirements
Évaluation biologique des dispositifs médicaux résorbables —
Partie 1: Exigences générales
Reference number
©
ISO 2021
© ISO 2021
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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General considerations . 2
5 Test article considerations . 4
6 Sterilization considerations . 4
7 Drug-device combination product considerations . 4
8 E valuation of absorbable medical devices in the context of the ISO 10993 series .4
8.1 General . 4
8.2 ISO 10993-1, evaluation and testing within a risk management process . 5
8.3 ISO 10993-2, animal welfare requirements . 5
8.4 ISO 10993-3, tests for genotoxicity, carcinogenicity, and reproductive toxicity . 5
8.5 ISO 10993-4, selection of tests for interactions with blood . 6
8.6 ISO 10993-5, tests for in vitro cytotoxicity . 6
8.7 ISO 10993-6, Tests for local effects after implantation . 6
8.8 ISO 10993-7, ethylene oxide sterilization residuals . 7
8.9 ISO 10993-9, framework for identification and quantification of potential
degradation products . 7
8.10 ISO 10993-10, tests for skin sensitization. 7
8.11 ISO 10993-11, tests for systemic toxicity . 7
8.12 ISO 10993-12, sample preparation and reference materials . 8
8.13 ISO 10993-13, identification and quantification of degradation products from
polymeric medical devices . 8
8.14 ISO 10993-14, identification and quantification of degradation products from ceramics . 8
8.15 ISO 10993-15, identification and quantification of degradation products from
metals and alloys . 9
8.16 ISO 10993-16, toxicokinetic study design for degradation products and leachables . 9
8.17 ISO 10993-17, establishment of allowable limits for leachable substances . 9
8.18 ISO 10993-18, chemical characterization of materials . 9
8.19 ISO/TS 10993-19, physico-chemical, morphological and topographical
characterization of materials . 9
8.20 ISO/TS 10993-20, principles and methods for immunotoxicology testing of
medical devices .10
8.21 ISO/TR 10993-22, guidance on nanomaterials .10
8.22 ISO 10993-23, tests for irritation .10
8.22.1 General.10
8.22.2 Tests for irritation .10
Annex A (informative) Nomenclature of absorb, degrade and related terms .11
Bibliography .12
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 194, Biological and clinical evaluation of
medical devices.
A list of all parts in the ISO 37137 series can be found on the ISO website.
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 2021 – All rights reserved
Introduction
Absorbable implants are intentionally designed to degrade and therefore release degradation products
into the patient, a feature making these products fundamentally different from other medical devices
that are not intended to be absorbed by the patient’s body.
The provided content is intended to describe potential approaches to perform biological evaluation of
absorbable implants to support the safety of such absorbable medical devices.
TECHNICAL SPECIFICATION ISO/TS 37137-1:2021(E)
Biological evaluation of absorbable medical devices —
Part 1:
General requirements
1 Scope
This document specifies the requirements for the evaluation of absorbable medical devices during
a biological risk assessment based on ISO 10993-1, including a clarification of the terms "absorb",
"degrade" and other related terms (see Annex A).
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 10993 (all parts), Biological evaluation of medical devices
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/
NOTE For further discussion of utilized terminology and for a list of potential terms to be included in a
literature search see Annex A.
3.1
absorb
absorption
action of a non-endogenous (foreign) material or substance, or its decomposition
products passing through or being assimilated by either cells or tissue, or both over time
[SOURCE: ISO 10993-6:2016, 3.1]
3.2
degradation product
intermediate or final substance which results from the physical, metabolic, and/or chemical
decomposition of a material or agent
3.3
degrade
physically, metabolically, and/or chemically decompose a material or substance
3.4
leachable
substance that can be released from a medical device or material during clinical use or simulated
clinical use
Note 1 to entry: In absorbable medical devices, leachables can be substances released from the as-manufactured
product or substances generated and released as a consequence of its degradation (i.e. degradation products).
[SOURCE: ISO 10993-12:2020, 3.9 modified — Note 1 to entry has been added.]
3.5
final product
medical device or medical device component that has been subjected to all manufacturing processes for
the “to be marketed” medical device including packaging and if applicable, sterilization
Note 1 to entry: The final medical device or sterilized finished medical device has the same meaning as the final
product in this document.
[SOURCE: ISO 10993-1:2018, 3.8 modified — Note 1 to entry has been added.]
4 General considerations
Biological evaluation is the assessment of a medical device, medical device component, or a material
to determine if either the medical device material or the medical device design, or both is likely to
result in an unacceptable adverse systemic and/or local effect on the surrounding cells and/or tissues.
Biological evaluation of an absorbable material shall be conducted in accordance with ISO 10993-1, and
other relevant parts of ISO 10993. Any modifications to the methods specified in the ISO 10993 series of
standards shall be justified in a written biological risk assessment.
Degradation products can be released into either the extraction media or tissue, or both or remain in
the degrading implant. Released degradation products that are generated either prior to product use
(i.e. during manufacturing, processing or shelf-life) or during product use should be characterized (e.g.
chemical identity, quantity, toxicity, and particulates (see 8.19) as applicable).
Identification of the degradation products may be derived from chemical and physical analyses of the
implant or through a theoretical judgement. Literature data for implants manufactured from absorbable
materials with an established history of safe clinical use (at the intended anatomical location) can be
helpful in identifying expected degradation products and potential toxicities if there is an adequate
...
TECHNICAL ISO/TS
SPECIFICATION 37137-1
First edition
2021-03
Biological evaluation of absorbable
medical devices —
Part 1:
General requirements
Évaluation biologique des dispositifs médicaux résorbables —
Partie 1: Exigences générales
Reference number
©
ISO 2021
© ISO 2021
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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General considerations . 2
5 Test article considerations . 4
6 Sterilization considerations . 4
7 Drug-device combination product considerations . 4
8 E valuation of absorbable medical devices in the context of the ISO 10993 series .4
8.1 General . 4
8.2 ISO 10993-1, evaluation and testing within a risk management process . 5
8.3 ISO 10993-2, animal welfare requirements . 5
8.4 ISO 10993-3, tests for genotoxicity, carcinogenicity, and reproductive toxicity . 5
8.5 ISO 10993-4, selection of tests for interactions with blood . 6
8.6 ISO 10993-5, tests for in vitro cytotoxicity . 6
8.7 ISO 10993-6, Tests for local effects after implantation . 6
8.8 ISO 10993-7, ethylene oxide sterilization residuals . 7
8.9 ISO 10993-9, framework for identification and quantification of potential
degradation products . 7
8.10 ISO 10993-10, tests for skin sensitization. 7
8.11 ISO 10993-11, tests for systemic toxicity . 7
8.12 ISO 10993-12, sample preparation and reference materials . 8
8.13 ISO 10993-13, identification and quantification of degradation products from
polymeric medical devices . 8
8.14 ISO 10993-14, identification and quantification of degradation products from ceramics . 8
8.15 ISO 10993-15, identification and quantification of degradation products from
metals and alloys . 9
8.16 ISO 10993-16, toxicokinetic study design for degradation products and leachables . 9
8.17 ISO 10993-17, establishment of allowable limits for leachable substances . 9
8.18 ISO 10993-18, chemical characterization of materials . 9
8.19 ISO/TS 10993-19, physico-chemical, morphological and topographical
characterization of materials . 9
8.20 ISO/TS 10993-20, principles and methods for immunotoxicology testing of
medical devices .10
8.21 ISO/TR 10993-22, guidance on nanomaterials .10
8.22 ISO 10993-23, tests for irritation .10
8.22.1 General.10
8.22.2 Tests for irritation .10
Annex A (informative) Nomenclature of absorb, degrade and related terms .11
Bibliography .12
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 194, Biological and clinical evaluation of
medical devices.
A list of all parts in the ISO 37137 series can be found on the ISO website.
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 2021 – All rights reserved
Introduction
Absorbable implants are intentionally designed to degrade and therefore release degradation products
into the patient, a feature making these products fundamentally different from other medical devices
that are not intended to be absorbed by the patient’s body.
The provided content is intended to describe potential approaches to perform biological evaluation of
absorbable implants to support the safety of such absorbable medical devices.
TECHNICAL SPECIFICATION ISO/TS 37137-1:2021(E)
Biological evaluation of absorbable medical devices —
Part 1:
General requirements
1 Scope
This document specifies the requirements for the evaluation of absorbable medical devices during
a biological risk assessment based on ISO 10993-1, including a clarification of the terms "absorb",
"degrade" and other related terms (see Annex A).
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 10993 (all parts), Biological evaluation of medical devices
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/
NOTE For further discussion of utilized terminology and for a list of potential terms to be included in a
literature search see Annex A.
3.1
absorb
absorption
action of a non-endogenous (foreign) material or substance, or its decomposition
products passing through or being assimilated by either cells or tissue, or both over time
[SOURCE: ISO 10993-6:2016, 3.1]
3.2
degradation product
intermediate or final substance which results from the physical, metabolic, and/or chemical
decomposition of a material or agent
3.3
degrade
physically, metabolically, and/or chemically decompose a material or substance
3.4
leachable
substance that can be released from a medical device or material during clinical use or simulated
clinical use
Note 1 to entry: In absorbable medical devices, leachables can be substances released from the as-manufactured
product or substances generated and released as a consequence of its degradation (i.e. degradation products).
[SOURCE: ISO 10993-12:2020, 3.9 modified — Note 1 to entry has been added.]
3.5
final product
medical device or medical device component that has been subjected to all manufacturing processes for
the “to be marketed” medical device including packaging and if applicable, sterilization
Note 1 to entry: The final medical device or sterilized finished medical device has the same meaning as the final
product in this document.
[SOURCE: ISO 10993-1:2018, 3.8 modified — Note 1 to entry has been added.]
4 General considerations
Biological evaluation is the assessment of a medical device, medical device component, or a material
to determine if either the medical device material or the medical device design, or both is likely to
result in an unacceptable adverse systemic and/or local effect on the surrounding cells and/or tissues.
Biological evaluation of an absorbable material shall be conducted in accordance with ISO 10993-1, and
other relevant parts of ISO 10993. Any modifications to the methods specified in the ISO 10993 series of
standards shall be justified in a written biological risk assessment.
Degradation products can be released into either the extraction media or tissue, or both or remain in
the degrading implant. Released degradation products that are generated either prior to product use
(i.e. during manufacturing, processing or shelf-life) or during product use should be characterized (e.g.
chemical identity, quantity, toxicity, and particulates (see 8.19) as applicable).
Identification of the degradation products may be derived from chemical and physical analyses of the
implant or through a theoretical judgement. Literature data for implants manufactured from absorbable
materials with an established history of safe clinical use (at the intended anatomical location) can be
helpful in identifying expected degradation products and potential toxicities if there is an adequate
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.