ISO/TS 17137:2019

TECHNICAL ISO/TS
SPECIFICATION 17137
Second edition
2019-09
Cardiovascular implants and
extracorporeal systems —
Cardiovascular absorbable implants
Implants cardiovasculaires et systèmes extracorporels — Implants
cardiovasculaires absorbables
Reference number
©
ISO 2019
© ISO 2019
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
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved

Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Device design, fabrication, packaging, and use considerations . 2
4.1 Classification . 2
4.2 Intended clinical performance . 3
4.3 Intended clinical use . 3
4.4 Materials . 3
4.5 Packaging, labelling, and sterilization . 4
4.5.1 Packaging. 4
4.5.2 Labelling . 4
4.5.3 Sterilization . 5
4.6 Product shelf-life considerations . 6
4.6.1 General information . 6
4.6.2 Real-time aging. 7
4.6.3 Accelerated aging . 7
4.7 Risk management . 7
4.7.1 General. 7
4.7.2 Failure modes . 7
4.7.3 Risk mitigation . . 8
4.7.4 Specific aspects for absorbable implants . 8
5 Design evaluation . 8
5.1 E valuation overview and general considerations . 8
5.1.1 Overview . 8
5.1.2 General considerations .10
5.1.3 Summary of in vitro evaluation steps .11
5.2 in vitro procedural evaluation .12
5.2.1 Conditioning of test samples .12
5.2.2 Assessment of delivery and placement .12
5.2.3 Assessment of initial function post-deployment .13
5.3 in vitro degradation evaluation .13
5.3.1 General.13
5.3.2 Sample conditioning .14
5.3.3 Mechanical evaluation.14
5.3.4 Cyclic fatigue durability evaluation .15
5.3.5 Physical/chemical degradation evaluation .15
5.3.6 Imaging compatibility evaluation .17
5.4 Biological evaluation .17
5.4.1 General considerations .17
5.4.2 Sterilization considerations .18
5.4.3 Drug-device combination product considerations .18
5.5 in vitro-in vivo correlation .19
5.6 in vivo pre-clinical evaluation .19
5.6.1 Purpose .19
5.6.2 Specific objectives .20
5.6.3 Protocol .20
5.6.4 Data collection .22
5.6.5 Test report and additional information .22
5.7 Clinical evaluation .22
5.7.1 Purpose .22
5.7.2 Specific objectives .23
5.7.3 Clinical investigation plan .23
5.7.4 Data collection .23
5.7.5 Final report .24
5.7.6 Post market surveillance.24
Annex A (informative) Explanation on nomenclature of absorb, degrade and related terms .25
Bibliography .26
iv © ISO 2019 – All rights reserved

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, Subcommittee
SC 2, Cardiovascular implants and extracorporeal systems.
This second edition cancels and replaces the first edition (ISO/TS 17137:2014), which has been
technically revised.
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.
Introduction
Absorbable cardiovascular implants are medical devices with various clinical indications for use in
the human cardiovascular blood system. An absorbable cardiovascular implant, or at least a portion
thereof, is designed to intentionally degrade over time into degradation products that are absorbed by
the body through metabolism, assimilation, and/or excretion (elimination). Such implants can be either
surgically or interventionally introduced to the site of treatment.
This document outlines requirements for intended performance, design attributes, materials, design
evaluation, manufacturing, sterilization, packaging, and information supplied by the manufacturer. This
document should be considered as a supplement to ISO 14630, which specifies general requirements
for the performance of non-active surgical implants. This document should also be considered as a
supplement to relevant device-specific standards such as the ISO 25539 series specifying requirements
for endovascular devices, which do not address degradation and other time dependent aspects of
absorbable implants and coatings. Additionally, this document should be considered in conjunction
with ISO 14155, which specifies proper practices in clinical investigations.
This document is not comprehensive with respect to the pharmacological evaluation of cardiovascular
absorbable implants. More detailed safety and performance requirements for pharmacological agents
included in the absorbable cardiovascular implant are described in ISO 12417-1.
Only issues related to degradation and absorption combined with the cardiovascular implant are
covered by this document. Due to the variations in the design of implants covered by this document
and in some cases due to the relatively recent development of some of these implants (e.g. absorbable
stents), acceptable standardized in vitro tests and clinical results are not always available. As further
scientific and clinical data become available, appropriate revision of this document will be necessary.
NOTE For issues related to the common mechanical function of the cardiovascular implant, the reader might
find it useful to consider a number of other international standards (see Bibliography).
vi © ISO 2019 – All rights reserved

TECHNICAL SPECIFICATION ISO/TS 17137:2019(E)
Cardiovascular implants and extracorporeal systems —
Cardiovascular absorbable implants
1 Scope
This document outlines design evaluation guidelines for absorbable cardiovascular implants used
to treat vessels and/or the vascular space within the circulatory system, including the heart and all
vasculature. This document is meant to supplement device-specific standards by providing guidelines
specific for absorbable implants and/or components
This document is applicable to implants in direct contact with the cardiovascular system, where the
intended action is upon the circulatory system. This document does not address the specific evaluation
of issues associated with viable tissues, viable cells, and/or implants with non- viable biological materials
and their derivatives. Additionally, procedures and devices used prior to and following the introduction
of the absorbable cardiovascular implant (e.g. balloon angioplasty devices) are excluded from the
scope of This document if they do not affect the absorption aspects of the implant. A cardiovascular
absorbable implant may incorporate substance(s) which, if used separately, can be considered to be a
medicinal product (drug product) but the action of the medicinal substance is ancillary to that of the
implant and supports the primary mode of action of the implant.
NOTE 1 Some aspects of absorbable components of cardiovascular device-drug combination products (e.g.
coatings) in their connection with drug-related aspects of the device are addressed in ISO 12417-1.
NOTE 2 An explanation of the nomenclature of absorb, degrade and related terms can be found in Annex A of
this document.
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 5840 (all parts), Cardiovascular implants — Cardiac valve prostheses
ISO 10993 (all parts), Biological evaluation of medical devices
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137 (all parts), Sterilization of health care products — Radiation
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
ISO 12417-1, Cardiovascular implants and extracorporeal systems — Vascular device-drug combination
products — Part 1: General requirements
ISO 14155, Clinical investigation of medical devices for human subjects— Good clinical practice
ISO 14630, Non-active surgical implants — General requirements
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 25539 (all parts), Cardiovascular implants — Endovascular devices
ISO/TR 37137, Cardiovascular biological evaluation of medical devices —Guidance for absorbable implants
ASTM F640, Standard Test Methods for Determining Radiopacity for Medical Use
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/
3.1
absorb
absorption
action of a non-endogenous (foreign) material or substance or its degradation products
passing through or being assimilated by cells and/or tissue over time
3.2
degradation product
intermediate or final result from the physical, metabolic, and/or chemical decomposition of a material
or substance
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
Note 1 to entry: In absorbable 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).
4 Device design, fabrication, packaging, and use considerations
4.1 Classification
A cardiovascular absorbable implant is a product that accomplishes its intended clinical use and
performance through primarily physical and/or mechanical means over a defined time period. An
absorbable cardiovascular implant may also incorporate a medicinal substance. A cardiovascular
absorbable implant accomplishes its intended clinical use and is then fully or partially absorbed by the
body over a finite period of time. The implant’s temporary nature is provided by its ability to degrade
and the resulting degradation products’ ability to be metabolized, assimilated, and/or excreted
(eliminated) over time.
The manufacturer shall determine the acceptability of the product for clinical use at all stages of the
product life cycle.
2 © ISO 2019 – All rights reserved

4.2 Intended clinical performance
The intended performance of an absorbable implant shall be described and documented by addressing
at least the following, with particular regard to patient’s safety:
a) intended purpose(s);
b) functional lifetime – duration of intended mechanical function;
c) in vivo longevity – approximate time to full absorption of the absorbable components; absence of
histological (physical) presence in tissue.
4.3 Intended clinical use
The intended clinical use shall, if applicable, be preferentially identified as one or more of the following:
a) abdominal aorta;
b) arterio-venous shunt for vascular access;
c) carotid artery;
d) coronary artery;
e) coronary heart chambers;
f) femoral artery;
g) iliac artery;
h) popliteal artery;
i) intra-cerebral artery;
j) renal artery;
k) thoracic aorta;
l) thoraco-abdominal aorta;
m) tibial artery;
n) heart valve;
o) venous valve;
p) other heart, arterial, or venous anatomy to be specified as appropriate.
4.4 Materials
The requirements of ISO 14630:2012, Clause 6, shall apply.
Additional testing appropriate to specific material types (e.g. metals, polymers, drugs) shall be
performed to determine material acceptability for use in the design. For example, guidance for assessing
absorbable polymeric implants can be found in ASTM F2902, with ASTM F3160 useful for absorbable
metal materials testing. In a more specific example, absorbable materials dependent on shape memory
properties should be subjected to testing that assesses transformation properties. For drug-eluting
absorbable implants, drug identity testing shall be performed, including the identification of impurities
and degradants. Electro-chemical potentials of differing metals (stents, guidewires, other accessory
devices) might require additional types of testing.
4.5 Packaging, labelling, and sterilization
4.5.1 Packaging
4.5.1.1 General
The requirements of ISO 11607-1 and ISO 14630:2012, Clause 10 shall apply.
Each device shall be packaged in a unit container with a sterile barrier, or a combination of unit
container and an outer container. The unit container (within its outer container if applicable) may be
packaged in a shipping container during transit and storage.
The device packaging configuration should be designed to protect the implant during normal conditions
of handling, storage and transport such that device specifications are maintained. The sterile barrier
shall be maintained throughout its designated shelf-life to permit the contents to be presented for use
in an aseptic manner.
4.5.1.2 Considerations for absorbable product
For absorbable products, non-standard packaging attributes may be needed to mitigate or eliminate
the effects of environmental factors in order to maintain the physical, chemical and/or mechanical
specifications of the implant. Where the absorbable product is susceptible to hydrolytic or corrosive
degradation, consideration should be given toward the control and/or removal of moisture from the
package interior (e.g. through the use of moisture resistant packaging materials and/or desiccants).
In addition, absorbable products may also be susceptible to physical, chemical, and/or mechanical
degradation under extreme temperature conditions. For example, storage of polymeric products or
components at temperatures that approach or exceed a glass transition temperature could adversely
affect the physical and chemical state of the implant. Therefore, storage conditions should specify the
acceptable temperature range and limit the duration of packaged product exposure to elevated thermal
conditions.
4.5.2 Labelling
4.5.2.1 Label(s)
Each device shall be accompanied by one or more labels, one on each of the containers.
The requirements of ISO 14630:2012, Clause 11, shall apply, with the following information to be
supplied as part of the label(s):
a) name or trade name of the device;
b) expiration date (indication of shelf-life) and the recommended storage conditions;
c) description and/or list of the package contents;
d) size and device type, if applicable;
e) dimensions applicable for clinical use;
f) sterilization method and the notification “STERILE”, if applicable;
g) a warning against the use of the device if the package’s sterile barrier is damaged;
h) a written and/or “Do not resterilize” symbol warning against re-sterilizing and/or reusing the
device, if applicable;
i) reference to consult Instructions for Use for user information;
j) chemical nature of any storage medium in the unit container, with appropriate hazard warning.
4 © ISO 2019 – All rights reserved

4.5.2.2 Instructions for use (IFU)
The requirements of ISO 14630:2012, Clause 11, shall apply together with the following information to
be included:
a) name or trade name of the device;
b) recommendations for storage; the actual modelled storage range determined to be acceptable
for the packaged device, taking into consideration the absorbable properties of the implant or
components thereof;
c) statement that the device can or cannot be re-sterilized, including the statements “STERILE”, “DO
NOT RESTERILIZE” in prominent form, if applicable;
d) the statement “SINGLE USE ONLY” in prominent form;
e) description and/or list of the package contents;
f) available models and sizes applicable for intended clinical use;
g) identification and description of the absorbable device or components thereof;
h) location of the absorbable part of the device, if only a portion of the implant is absorbable;
i) a general description of the principle of degradation along with both the expected time frame for
loss of mechanical function and absorption of the implant;
j) intended use/indications for use;
k) contraindications, warnings and precautions;
l) the potential for interaction of the absorbable material with other materials used in the handling,
preparation and implantation of the implant, considering direct contact and the effect of
procedural fluids;
m) potential adverse events, including known adverse events associated with implant (or portion
thereof) degradation and/or in vivo absorption process;
n) recommended methods for the aseptic presentation and preparation of the implant considering the
potential for interaction of the absorbable material with the environment or materials used;
o) recommended methods for preparation of the implantation site if applicable;
p) recommendations for visualization if applicable;
q) if the implant is metallic, electrically conductive, or contains metallic or electrically conductive
components, MRI safety information shall be provided, including any potential impact that an
accompanying radio frequency (RF)-induced temperature rise may have on the absorbable
properties of the implant or components thereof. Provided information may also include a post-
implantation time period after which safety MRI precautions are no longer relevant or needed;
r) date of or reference relating to the publication of the text, indicating if the text has been revised.
4.5.3 Sterilization
4.5.3.1 General
The sterilization requirements of ISO 14630 shall apply.
The entirety of the device and packaging shall be compatible with the chosen sterilization method. The
following provides a list of typical sterilization methods and a brief description of their applicability to
absorbable implants or components thereof.
4.5.3.2 Radiation sterilization
If devices are to be sterilized by gamma, electron beam or X-ray radiation sterilization, ISO 11137-1,
-2, -3 shall apply, including the Part 1 provision that the product meet its performance specifications
throughout its intended lifetime at its maximum acceptable dose. Radiation sterilization processes in
polymers can generate free radicals and a potential for change in absorbable material properties that
could impact product performance.
4.5.3.3 Ethylene oxide sterilization
If devices are to be sterilized by ethylene oxide, ISO 11135 shall apply, including the provision that
the product meets its performance specifications at the most challenging parameters. Ethylene oxide
sterilization processes involve exposure to heat and humidity parameters that may impact absorbable
material properties that could impact product performance.
4.5.3.4 Steam sterilization
If devices are to be sterilized by steam, ISO 17665-1 shall apply. Steam may not be a viable sterilization
option for hydrolysable polymers that are highly susceptible to uncontrollable damage under autoclave
conditions.
4.5.3.5 Alternative sterilization
If devices are to be sterilized by use of any other sterilization method, such as dry heat sterilization,
hydrogen peroxide sterilization, ozone or nitrogen dioxide sterilization, ISO 14937 shall apply.
4.6 Product shelf-life considerations
4.6.1 General information
Shelf-life is the amount of time that a packaged product can be expected to be stored under specified
conditions and meet critical performance properties. Establishment of shelf-life should directly or
indirectly assess the device’s ability to meet its specified functional requirements upon its removal
from its packaging after appropriate storage. For absorbable devices, storage conditions can be vitally
important (e.g. temperature and humidity) and deserve careful consideration. A detailed understanding
of implant susceptibility to degradation under expected storage conditions is paramount to a successful
shelf-life program.
Establishment of product shelf-life shall be through evaluation of one or more appropriate implant
performance tests conducted on the final product, with justification for the selection of tests provided.
Refer to ASTM F2914 for guidance in selecting appropriate tests for the determination of shelf-life
in endovascular devices. If different finished product manufacturing sites are used, generation of
appropriate batch release/stability data including appropriate performance specifications to ensure
the consistency and equivalency of the finished product across manufacturing sites should also be
considered.
ISO/IEC Guide 51, ISO/IEC Guide 63, ISO 10993-1, and ISO 11135 (see Clause 2 and the Bibliography)
provide guidance regarding shelf-life establishment. It is often unnecessary to assess every device
attribute measured at time 0 (i.e. no aging) and after appropriate storage conditions to establish
shelf-life. ASTM F2914 provides guidance for determination of the appropriate attributes for testing
as part of establishment of shelf-life for endovascular devices. Accelerated aging might be appropriate
to establish the shelf-life of an absorbable device in a timely manner. AAMI TIR17 contains guidance
regarding accelerated aging programs and provides a brief discussion of aging theory. Also, ASTM
F1980 provides guidance on accelerated aging parameters and discusses humidity. Absorbable device
shelf-life establishment requires special consideration. ASTM F2902 provides guidance regarding shelf-
life of absorbable polymeric implants.
6 © ISO 2019 – All rights reserved

4.6.2 Real-time aging
Shelf-life assessment of packaged and sterilized absorbable products should include real-time exposure
to temperature and humidity challenge conditions that, at minimum, are reflective of the expected
storage environment.
Guidance regarding transportation related performance evaluation is provided in 4.7.2.
Real-time testing of the absorbable device’s critical attributes under conditions analogous to actual
storage conditions is the most definitive means for assessing the shelf-life of a packaged absorbable
device. Multiple time points (e.g. 6, 12, and 24 months) are recommended to mitigate risk associated
with a failure to meet the requirements at later time points.
4.6.3 Accelerated aging
Accelerated aging allows medical devices to be provided to health care professionals with specified
shelf-life in a timely manner. However accelerated aging can lead to an inaccurate assessment of the
shelf-life of a product, providing additional risk to the patient. Thus, when accelerated aging programs
are designed, conservatism is recommended. Real-time aging studies should be conducted in addition
to the accelerated aging studies to validate the shelf-life established by accelerated aging testing.
The testing plan to establish the desired shelf-life of an absorbable device using accelerated conditions
should consider the mechanism of degradation of the implant. The rationale for the accelerated
aging factors should be provided. Conservative aging factors should be chosen. AAMI TIR17 provides
conservative accelerated aging factors. These conservative factors might not be appropriate for
absorbable devices and should be used with caution.
Exposure to humidity, ultraviolet light, ozone, or other gases can also be used to establish the shelf-
life of an absorbable device if the aging process of the materials can be shown to correlate with these
environmental factors. It should be noted that aging can be accelerated when multiple aging processes
are involved. One should carefully define the combined effect of accelerated aging in establishing the
protocol for these aging process validations.
4.7 Risk management
4.7.1 General
The manufacturer shall define and implement a risk management system in accordance with ISO 14971.
The entire system shall provide intended users the ability to safely and effectively perform all required
preoperative, intra-operative, and post-operative procedural tasks and achieve all desired objectives.
This shall include all other tools and accessories that intended users will use to complete the procedure.
NOTE For guidance on how to determine and establish design attributes pertaining to the use of the system
to conduct the implant procedure, see IEC 62366-1.
4.7.2 Failure modes
There exist three major categories of failure modes. Examples of possible failure within each category
specific to absorbable cardiovascular implants include the following:
Design related: One or more implant design deficiencies (e.g. materials, dimensions, construction)
can result in unintended functional failure (e.g. selection of an absorbable material that degrades
prematurely). In addition, implant design should provide a safety margin adequate to provide functional
integrity in all clinical indications (e.g. force differences in the coronary vs tibial artery).
Manufacturing related: Inappropriate manufacturing conditions (e.g. excess moisture), storage
(e.g. defective packaging) and/or transport (e.g. excess thermal exposure) can potentially result in
functional compromise or failure.
Application/User Interface related: Unintended (abnormal) use errors (e.g. over-expansion resulting
in excessive particulate/fragment generation at implantation) as described in IEC 62366-1. Intended
(correct) use errors (e.g. unable to deliver device past tortuous anatomy that was not excluded in the IFU).
NOTE The ISO 25539 series and the ISO 5840 series contain lists of potential cardiovascular hazards that
can provide basis for a risk analysis of an absorbable implant. Additional risk analysis guidance can be found in
ISO 10993-1, ISO/TR 37137 and ISO 14971.
4.7.3 Risk mitigation
These risks can be mitigated by three mechanisms (see also ISO 14971:2007, A.2.6.2):
a) inherent safety by design;
b) protective measures in the medical device itself or in the manufacturing process;
c) information for safety.
4.7.4 Specific aspects for absorbable implants
Absorbable implants exhibit time-dependent sensitivities to temperature and moisture due to the
degradable/corrosive nature of these implant materials. Therefore, the whole life span of the implant
from the raw material up to the complete absorption of the implant should be analysed carefully to
identify the potential for risk related to premature degradation during processing, distribution, and
implantation (see Figure 1). Potential approaches for mitigating such risks are discussed throughout
this document.
Figure 1 — Life span of one single device/implant
5 Design evaluation
5.1 E valuation overview and general considerations
5.1.1 Overview
A general characterization of the implant’s composition, structural features, and degradation properties
needs to be included in a design verification or validation. The relevant material and mechanical
properties of the as-manufactured implant should be characterized from their initial pre-implanted
8 © ISO 2019 – All rights reserved

state and at select time points during degradation until measurement of the partially degraded implant
becomes impractical. An overview of the assessment guidance provided herein is as follows:
— 4.6 covers shelf-life and product aging considerations (covered previously).
— 5.1 Summarizes the in vitro evaluation steps and describes general considerations and relevant pre-
test characterizations and treatments.
— 5.2 guides product assessment at timeframes based on package opening through vessel closure,
which includes the delivery, placement, and initial function of the device (depicted as Procedural
Stage in Figure 2).
— 5.3 addresses appropriate characterization of the post-procedure mechanical, dimensional, mass,
and chemical changes that occur as the implant (and any included coating) adjust to the physiological
environment and encounter degradation over time (depicted as the Intermediate Stage in Figure 2).
— 5.4 describes biocompatibility testing of absorbable implants, including reference to specific
guidance for testing in accordance with the various parts of ISO 10993.
— 5.5 discusses some of the issues and potential barriers to successful generation of a correlation
between in vitro and in vivo results.
— 5.6 covers both cardiovascular and absorbable specific concerns when conducting a pre- clinical in
vivo evaluation.
— 5.7 covers absorbable-specific concerns when conducting a clinical evaluation.
Figure 2 — Schematic representation of stages in the degradation of an absorbable implant
Degradation of the implant should be characterized in vitro at multiple time points that encompass the
timeframe for implantation (“Procedural Stage”), active degradation (“Intermediate Stage”), and the
expected final in vivo histological disappearance of the absorbable implant or component (“Advanced
Stage”). Attributes representing relevant chemical, physical, and mechanical degradation should be
monitored. In this example figure, the decline in mechanical attributes is schematically represented.
The degradation profile for some materials may exhibit alternate trends but generally will include a
decay to measurement limits. Acceptance criteria (shown as yellow triangles in Figure 2) at multiple
relevant time points can be defined based on the needs of the end user and requirements of the device
for treatment. Examples for how the degradation profile may compare to select acceptance criteria are
shown. Also, as degradation proceeds it is likely that the attribute being measured will approach or
coincide with measurement limits in the Advanced Stage.
NOTE Certain device attributes can only be measured as long as the sample has adequate structural
integrity. For example, a stent in the advanced stage will likely disintegrate upon movement, although it may
retain its dimensions when surrounded by tissue in vivo.
5.1.2 General considerations
A non-exhaustive listing of material and implant characteristics that should be considered for inclusion
and subsequent assessment are:
a) Composition/chemical/purity properties (e.g. molecular weight, inherent viscosity), thermal
properties (e.g. polymeric Tg, melting point), and microstructure [e.g. degree of crystallinity (in
polymers), grain size (in metals), pore characterization (in porous constructs)];
b) Corrosion/degradation mechanism and rate profiling, including consideration of potential
variations and/or material interactions in different applicable environments (e.g. extreme storage
or in vivo service conditions);
c) Changes that occur over the lifetime of the implant with respect to its chemical, thermal, and/or
physical properties (e.g. molecular weight, mass), as well as the implant’s mechanical behaviour
and degradation products;
NOTE 1 Degradation products may be released into the media/tissue or reside in the degrading implant.
Released degradation products that are generated either prior to product use (i.e. during processing or
shelf- life) or during degradation should be characterized (e.g. chemical identity, quantity, and toxicity).
Identification of the degradation products may be derived from chemical analyses of the implant or in
some cases a theoretical analysis. Literature data for implants manufactured from absorbable materials
with an established history of safe clinical use (e.g. PGA) at the intended location may be helpful in
identifying expected degradation products and potential toxicities – if one can demonstrate that
equivalent manufacturing processes were used. A toxicological risk assessment of degradation products
over time in conjunction with toxicity data from the literature may be sufficient to support an omission
of biocompatibility testing from various stages of material degradation (either during device storage or in
clinical use).
NOTE 2 Guidance regarding the identification and assessment of chemical degradation products and
leachables can be found in ISO 10993-9 and 17.
d) Integrity of the implant under both n
...