(cid:40)(cid:91)(cid:75)(cid:76)(cid:69)(cid:76)(cid:87)(cid:3)200(cid:22)(cid:3)
`
`

`

`Waters Techs. Corp. v. Biomedical Device Consultants & Labs
`IPR2018-00498
`Ex. 2003
`
`Page 1 of 128
`
`

`

`Objectives and uses of AAMI standards and
`recommended practices
`
`It is most important that the objectives and potential uses of an
`AAMI product standard or recommended practice are clearly
`understood. The objectives of AAMI's technical development
`program derive from AAMI's overall mission: the advancement of
`medical instrumentation. Essential to such advancement are (1) a
`continued increase in the safe and effective application of current
`technologies to patient care, and (2) the encouragement of new
`technologies. It is AAMI's view that standards and recommended
`practices can contribute significantly to the advancement of
`medical
`instrumentation, provided that
`they are drafted with
`attention to these objectives and provided that arbitrary and
`restrictive uses are avoided.
`A voluntary standard for a medical device recommends to the
`manufacturer the information that should be provided with or on
`the product, basic safety and performance criteria that should be
`considered in qualifying the device for clinical use, and the
`measurement techniques that can be used to determine whether the
`device conforms with the safety and performance criteria and/or to
`compare the performance characteristics of different products.
`Some standards emphasize the information that should be provided
`with the device, including performance characteristics, instructions
`for use, warnings and precautions, and other data considered
`important in ensuring the safe and effective use of the device in the
`clinical
`environment.
`Recommending
`the
`disclosure
`of
`performance characteristics often necessitates the development of
`specialized test methods to facilitate uniformity in reporting;
`reaching consensus on these tests can represent a considerable part
`of committee work. When a drafting committee determines that
`clinical concerns warrant the establishment of minimum safety and
`performance criteria, referee tests must be provided and the reasons
`for establishing the criteria must be documented in the rationale.
`A recommended practice provides guidelines for the use, care,
`and/or processing of a medical device or system. A recommended
`practice does not address device performance per se, but rather
`procedures and practices that will help ensure that a device is used
`safely and effectively and that its performance will be maintained.
`Although a device standard is primarily directed to the
`manufacturer, it may also be of value to the potential purchaser or
`user of the device as a frame of reference for device evaluation.
`Similarly, even though a recommended practice is usually oriented
`towards healthcare professionals,
`it may be useful
`to the
`manufacturer in better understanding the environment in which a
`medical device will be used. Also, some recommended practices,
`while not
`addressing device performance
`criteria, provide
`guidelines to industrial personnel on such subjects as sterilization
`processing, methods of collecting data to establish safety and
`efficacy, human engineering, and other processing or evaluation
`techniques;
`such guidelines may be useful
`to health care
`professionals in understanding industrial practices.
`In determining whether an AAMI standard or recommended
`practice is relevant to the specific needs of a potential user of the
`document, several important concepts must be recognized:
`All AAMI standards and recommended practices are voluntary
`(unless, of course, they are adopted by government regulatory or
`procurement
`authorities). The application of a
`standard or
`recommended practice
`is
`solely within the discretion and
`pip/{islslional judgment of the user of the document.
`Single user license provided to AAMI standards committee members.
`
`Each AAMI standard or recommended practice reflects the
`collective expertise of a committee of health care professionals and
`industrial
`representatives, whose work has been
`reviewed
`nationally (and sometimes internationally). As such, the consensus
`recommendations embodied in a standard or recommended practice
`are intended to respond to clinical needs and, ultimately, to help
`ensure patient safety. A standard or recommended practice is
`limited, however,
`in the sense that
`it
`responds generally to
`perceived risks and conditions that may not always be relevant to
`specific situations. A standard or recommended practice is an
`important reference in responsible decision-making, but it should
`never replace responsible decision-making.
`Despite periodic review and revision (at least once every five
`years), a standard or recommended practice is necessarily a static
`document applied to a dynamic technology. Therefore, a standards
`user must carefiilly review the reasons why the document was
`initially developed and the specific rationale for each of its
`provisions. This review will reveal whether the document remains
`relevant to the specific needs of the user.
`Particular care should be taken in applying a product standard
`to existing devices and equipment, and in applying a recommended
`practice to current procedures and practices. While observed or
`potential risks with existing equipment typically form the basis for
`the safety and performance criteria defined in a
`standard,
`professional judgment must be used in applying these criteria to
`existing equipment. No single source of information will serve to
`identify a particular product as "unsafe". A voluntary standard can
`be used as one resource, but the ultimate decision as to product
`safety and efficacy must
`take into account
`the specifics of its
`utilization and, of course, cost-benefit considerations. Similarly, a
`recommended practice should be analyzed in the context of the
`specific needs and resources of the individual institution or firm.
`Again,
`the rationale accompanying each AAMI standard and
`recommended practice is an excellent guide to the reasoning and
`data underlying its provision.
`In summary, a standard or recommended practice is truly
`useful only when it is used in conjunction with other sources of
`information and policy guidance and in the context of professional
`experience and judgment.
`
`INTERPRETATIONS OF AAMI STANDARDS
`AND RECOMMENDED PRACTICES
`
`Requests for interpretations of AAMI standards and recommended
`practices must be made in writing, to the AAMI Vice President,
`Standards Policy and Programs. An official interpretation must be
`approved by letter ballot of the originating committee and
`subsequently reviewed and approved by the AAMI Standards
`Board. The interpretation will become official and representation of
`the Association only upon exhaustion of any appeals and upon
`publication of notice of interpretation in the "Standards Monitor"
`section of the AAMI News. The Association for the Advancement
`of Medical
`Instrumentation disclaims
`responsibility for any
`characterization or explanation of a standard or recommended
`practice which has not been developed and communicated in
`accordance with this procedure and which is not published, by
`appropriate notice, as an official interpretation in the AAMI News.
`
`Page 2 of 128
`
`Page 2 of 128
`
`

`

`American National Standard
`
`ANSI/AAMl/ISO 5840-3:2013
`
`Cardiovascular implants — Cardiac valve prostheses
`— Part 3: Heart valve substitutes implanted by
`transcatheter techniques
`
`Approved 23 November 2012 by
`Association for the Advancement of Medical Instrumentation
`
`Approved 4 December 2012 by
`American National Standards Institute
`
`Abstract:
`
`Outlines an approach for verifying/validating the design and manufacture of a transcatheter heart
`valve substitute through risk management. The selection of appropriate verification/validation tests
`and methods are to be derived from the risk assessment. The tests may include those to assess
`the physical, chemical, biological and mechanical properties of heart valve substitutes and of their
`materials and components. The tests can also include those for preclinical in vivo evaluation and
`clinical evaluation of the finished heart valve substitute.
`
`Keywords:
`
`design, hydrodynamic, material, performance, preclinical, risk, verification, structural
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`Page 3 of 128
`
`Page 3 of 128
`
`

`

`AAMI Standard
`
`This Association for the Advancement of Medical Instrumentation (AAMI) standard implies a consensus of those
`substantially concerned with its scope and provisions. The existence of an AAMI standard does not in any respect
`preclude anyone, whether they have approved the standard or not, from manufacturing, marketing, purchasing, or
`using products, processes, or procedures not conforming to the standard. AAMI standards are subject to periodic
`review, and users are cautioned to obtain the latest editions.
`
`CAUTION NOTICE: This AAMI standard may be revised or withdrawn at any time. AAMI procedures require that
`action be taken to reaffirm, revise, or withdraw this standard no later than 5 years from the date of publication.
`Interested parties may obtain current information on all AAMI standards by calling or writing AAMI, or by visiting the
`AAMI website at ,www.aami.org..
`
`All AAMI standards, recommended practices, technical information reports, and other types of technical documents
`developed by AAMI are voluntary, and their application is solely within the discretion and professional judgment of the
`user of the document. Occasionally, voluntary technical documents are adopted by government regulatory agencies
`or procurement authorities,
`in which case the adopting agency is responsible for enforcement of its rules and
`regulations.
`
`Published by
`
`Association for the Advancement of Medical Instrumentation
`4301 N. Fairfax Drive, Suite 301
`Arlington, VA 22203-1633
`.www.aami.org.
`
`© 2013 by the Association for the Advancement of Medical Instrumentation
`
`All Rights Reserved
`
`This publication is subject to copyright claims of ISO, ANSI, and AAMI. No part of this publication may be reproduced
`or distributed in any form, including an electronic retrieval system, without the prior written permission of AAMI. All
`requests pertaining to this document should be submitted to AAMI. It is illegal under federal law (17 U.S.C. § 101, et
`seq.) to make copies of all or any part of this document (whether internally or externally) without the prior written
`permission of the Association for the Advancement of Medical Instrumentation. Violators risk legal action, including
`civil and criminal penalties, and damages of $100,000 per offense. For permission regarding the use of all or any part
`of this document, complete the reprint request form at .www.aami.org. or contact AAMI at 4301 N. Fairfax Drive, Suite
`301, Arlington, VA 22203-1633. Phone: +1-703—525~4890; Fax: +1-703-525-1067.
`
`Printed in the United States of America
`
`ISBN 1-57020-492—6
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`Page 4 of 128
`
`Page 4 of 128
`
`

`

`Contents
`
`Page
`
`Glossary of equivalent standards
`
`Committee representation
`.....vii
`
`Background
`
`..vii
`
`Foreword................................................................................................................................................
`
`.....ix
`
`Introduction
`
`MIX
`
`‘J‘InhWNA
`
`Scope
`....1
`
`Normative references
`
`...1
`
`Terms anddefinitions
`
`3
`
`Abbreviations
`
`Fundamental reqUIrements
`
`11
`
`....11
`
`6
`6.1
`
`11
`Device description
`.11
`IntendedUse
`......12
`Design inputs
`6. 2
`12
`6.2.1 Operational specifications
`13
`6.2.2
`Performancespecifications........................................................................................................
`......15
`6.2.3 lmplantprocedure
`15
`6.2.4
`Packaging, labeling and sterIlIzatIon
`15
`
`6.3
`Design outputs...
`.....15
`6.4
`Design transfer (manufactunng verIfIcatIonlvalIdatIon)
`15
`6.5
`Risk management..
`.... .......
`
`....
`
`7.2.9
`
`Simulateduse..
`
`7.2.10 Human factors/usability assessment.
`7.3
`Preclinical in vivo evaluation...
`
`Overall requirements
`7.3.1
`7.3.2 Methods
`
`16
`Design verification testing and analysis/design validation
`7
`16
`General requirements
`7.1
`16
`In vitro assessment...
`......
`7.2
`16
`Test conditions, sample selection and reporting requirements...
`7.2.1
`17
`7.2.2 Materialpropertyassessment...
`18
`7.2.3 Device hydrodynamic performance assessment"
`. 20
`7.2.4
`Structural performance assessment"
`... ... ...
`22
`7.2.5 Additional implant design evaluation requirements
`23
`7.2.6 Delivery system design evaluation requirements
`24
`7.2.7 Design-specifictestIng
`25
`25
`25
`25
`25
`27
`28
`29
`29
`29
`30
`30
`30
`30
`
`Test report
`7.3.3
`Clinical InvestIgatIons
`7.4
`7_4_1 General"
`......... ......
`...............................................................H...H..............m..m..m
`7.4.2
`Statisticalconsiderations. ................ ..
`
`7.4.3 Distribution of subjectsand investigators-m..
`
`Sample sIze
`7.4.4
`7.4.5 EntrycrIterIa
`7.4.6 Duration of thestudy
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`Page 5 of 128
`
`Page 5 of 128
`
`

`

`7.4.7
`7.4.8
`
`Clinical data requirements31
`Clinical investigation report33
`
`Annexes
`
`Annex A (informative) Rationale for the provisions of this part of ISO 5840
`
`Annex B (informative) Examples of transcatheter heart valve substitutes, components and
`delivery systems
`
`35
`
`38
`
`AnnexC (normative) Packaging44
`
`Annex D (normative) Product labels, instructions for use and training45
`
`Annex E (normative) Sterlllzatlon49
`
`Annex F (informative) Valve description50
`
`Annex G (informative) Transcatheter heart valve substitute hazards, associated failure
`modes and evaluation methods52
`
`Annex H (informative) In vitro test guidelines for paediatric devices
`
`57
`
`Annex I (informative) Statistical procedures when using performance criteria................................62
`
`Annex J (informative) Examples and definitions of some physical and material properties of
`transcatheter heart valve substitutes and their components
`
`Annex K (informative) Examples of standards applicable to testing of materials and
`components of transcatheter heart valve substitutes
`
`63
`
`78
`
`Annex L (informative) Raw and post-conditioning mechanical properties for support
`structurematerlals 85
`
`Annex M (informative) Corrosion assessment87
`
`Annex N (informative) Guidelines for verification of hydrodynamic performance........................... 90
`
`Annex 0 (informative) Durability testing
`
`94
`
`Annex P (informative) Fatigue assessment96
`
`Annex Q (informative) Preclinical in vivo evaluation 103
`
`Annex R (normative) Adverse event classification during clinical investigation
`
`106
`
`Annex S (informative) Echocardiographic protocol 112
`
`Bibliography 115
`
`Figures
`
`Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one
`cycle4
`
`Figure 2 — Schematic representation of the positive pressure period of an aortic forward
`flow interval
`
`9
`
`Figure 3.1— ExampleA 38
`
`Figure 3.2 — ExampleB 39
`
`Figure 3.3 — ExampleC 39
`
`Figure 3.4 — ExampleD40
`
`Figure 3-5 -— ExampleE40
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`Page 6 of 128
`
`Page 6 of 128
`
`

`

`Figure 8.6 -— ExampleF41
`
`Figure 3.7 — Example G41
`
`Figure B.8 -— ExampleH42
`
`Figure 3.9 — Example I42
`
`Figure 3.10 —- Example J43
`
`Figure B.11— ExampleK43
`
`Figure J.1 — Example DSC graph for single-stage transformation nickel-titanium alloy................. 72
`
`Figure J.2 — Typical stress-strain curve of superelastic (SE) nitinol indicating various
`reportable parameters74
`
`Figure J.3 — Force-diameter curve of a superelastic (SE) nitinol support structure
`demonstrating chronic outward force (COF) and radial resistive force (RRF) 76
`
`Figure P.1 — Example schematic of a structural component fatigue assessment using a
`stress-or strain-life approach
`
`Tables
`
`Table 1 —— Heart valve substitute operational environment for left side of heart — Adult
`population
`
`96
`
`12
`
`Table 2 — Heart valve substitute operational environment for right side of heart — Adult
`populat|on,,.,,,.. 13
`
`Table 3 — Minimum device performance requirements, aortic
`
`Table 4—Minimum device performance requirements, mitral
`
`18
`
`19
`
`Table 6.1 — Transcatheter heart valve substitute hazards, associated failure modes and
`evaluation methods52
`
`Table H.1 — Pediatricdeflnltlons 57
`
`Table H.2 — Pulsatile flow test conditions: leftSide 58
`
`Table H.3 — Pulsatile flow test conditions: right side
`
`58
`
`Table H.4 —- Steady back pressure and forward flow conditions: left sude 59
`
`Table H.5 — Steady back pressure and forward flow conditions: right side
`
`59
`
`Table H.6 — AWT test conditions: leftSlde 60
`
`Table H.7 — AWT test conditions: rightSide so
`
`Table H.8 — FEA/life analysis conditions: leftsnde 61
`
`Table H.9 — FEAllife analysis conditions: right side
`
`Table Q.1—Examples of evaluations
`
`61
`
`104
`
`Table R.1——Examples of adverse events clinical outcome severity ranking 110
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`Page 7 of 128
`
`Page 7 of 128
`
`

`

`Glossary of equivalent standards
`
`International Standards adopted in the United States may include normative references to other International
`Standards. AAMI maintains a current list of each International Standard that has been adopted by AAMI (and ANSI).
`Available on the AAMI website at the address below, this list gives the corresponding U.S. designation and level of
`equivalency to the International Standard.
`
`www.aami.org/standards/glossagg.gdf
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`vi
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMI/ISO 5840-322013
`
`Page 8 of 128
`
`Page 8 of 128
`
`

`

`Committee representation
`
`Association for the Advancement of Medical Instrumentation
`
`Cardiac Valve Committee
`
`The adoption of ISO 5840-3:2013 as an American National Standard was initiated by the AAMI Cardiac Valve
`Committee. The AAMI Cardiac Valve Committee also functions as a US. Technical Advisory Group to the relevant
`work in the International Organization for Sterilization (ISO). U.S. representatives from the AAMI Cardiac Valve
`Committee (U.S. Sub-TAG for ISO/TC 150/SC 2/WG 1, Cardiac valves) played an active part in developing the ISO
`standard.
`
`At the time this document was published, the AAMI Cardiac Valve Committee had the following members:
`
`Cochairs:
`
`Members:
`
`Ann M. Graves
`Ajit Yoganathan, PhD
`
`Richard W. Bianco, University of Minnesota
`Jeffrey Borer, MD, Weill Cornell Medical College of Cornell University
`Lawrence Burr, MD, Vancouver, BC, Canada
`Robert Chang, Sadra Medical
`James C. Conti, PhD, Dynatek Labs
`Robert W.M. Frater, MD, Bronxville, NY
`Ann M. Graves St. Jude Medical
`Stephen Hilbert, PhD MD, Children‘s Mercy Hospital
`Timothy A. Kelley, Medtronic, Inc.
`Salvador Marquez, Edwards LifeSciences
`David Mester, W.L. Gore & Associates
`Keith Morel, DEKRA
`Stanton P. Nolan, MD, University of Virginia Health Sciences Center
`Jonas Runquist, HLT Inc.
`Hartzell Schaff, MD, Mayo Clinic
`Julie Selstrom, Direct Flow Medical, Inc.
`Sandy F. Stewart, PhD, Center for Devices and Radiological Health, US. Food and Drug
`Administration
`
`Craig Weinberg, PhD, Biomedical Device Consultants & Laboratories
`Julie Zaha, RN Southeastern Regional Medical Center
`Ajit Yoganathan, PhD, Georgia Institute of Technology
`
`Alternates:
`
`Lori Adels, BA PhD, Edwards LifeSciences
`Fernando Aguel, Center for Devices and Radiological Health, U.S. Food and Drug Administration
`Aaron Chalekian, St. Jude Medical Cardiovascular Division, Inc.
`Carol E. Eberhart, Medtronic, Inc.
`Helen Lavin, Sadra Medical
`Elaine, Strope, PhD, Dynatek Labs
`Steven L. Weinberg, PhD, Biomedical Device Consultants & Laboratories
`David Williams, RN MSN, W.L. Gore & Associates
`
`NOTE—Participation by federal agency representatives in the development of this standard does not constitute
`endorsement by the federal government or any of its agencies.
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMI/ISO 5840-32013
`
`vii
`
`Page 9 of 128
`
`Page 9 of 128
`
`

`

`Background of ANSI/AAMI adoption of ISO 5840-3:2013
`
`the International Organization for
`As indicated in the foreword to the main body of this document (page ix),
`Standardization (ISO) is a worldwide federation of national standards bodies. The United States is one of the ISO
`members that took an active role in the development of this standard, which was developed by ISO Technical
`Subcommittee 150/80 2, Cardiovascular implants and extracorporeal systems, to fill a need for standardization in the
`field of transcatheter heart valve substitutes.
`
`U.S. participation in this ISO SC is organized through the US. Technical Advisory Group for ISO/TC 150/80 2,
`administered by the Association for the Advancement of Medical Instrumentation (AAMI). The US. TAG for ISO/TC
`150/SC 2 supports the guidance provided in this document to select appropriate verification/validation tests and
`methods that are to be derived from risk assessment and define operational conditions and performance
`requirements where adequate scientific and/or clinical evidence exists for their justification.
`
`The US. adoption of ANSI/AAMl/ISO 5840-3z2013 was approved by the American National Standards Institute
`(ANSI) on 4 December 2012. The AAMI Cardiac Valve Committee (U.S. Sub-TAG for ISO/TC 150/SC 2NVG 1,
`Cardiac valves) initiated the US. adoption of ISO 5840-3:2013.
`
`AAMI and ANSI procedures require that standards be reviewed and, if necessary, revised every five years to reflect
`technological advances that may have occurred since publication.
`
`AAMI (and ANSI) have adopted other ISO standards. See the Glossary of Equivalent Standards for a list of ISO
`standards adopted by AAMI which gives the corresponding U.S. designation and the level of equivalency with the
`ISO standard.
`
`As used within the context of this document, “shall" indicates requirements strictly to be followed to conform to the
`standard. “Should" indicates that among several possibilities, one is recommended as particularly suitable, without
`mentioning or excluding others, or that a certain course of action is preferred but not necessarily required, or that (in
`the negative form) a certain possibility or course of action should be avoided but is not prohibited. “May” is used to
`indicate that a course of action is permissible within the limits of the standard. “Can” is used as a statement of
`possibility and capability. Finally, “must” is used only to describe “unavoidable" situations, including those mandated
`by government regulation.
`
`The concepts incorporated in this document should not be considered Inflexible or static. This standard, like any other,
`must be reviewed and updated periodically to assimilate progressive technological developments. To remain relevant,
`it must be modified as technological advances are made and as new data come to light.
`
`improving this document are invited. Comments and suggested revisions should be sent to
`Suggestions for
`Standards Department, AAMI, 4301 N. Fairfax Drive, Suite 301, Arlington, VA 22203-1633.
`
`
`
`NOTE—Beginning with the ISO foreword on page ix, this American National Standard is identical to ISO 5840-3:2013.
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`viii
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMI/ISO 5840-3z2013
`
`Page 10 of 128
`
`Page 10 of 128
`
`

`

`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. lSO
`collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
`electrotechnical standardization.
`
`International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
`
`International
`to prepare International Standards. Draft
`The main task of technical committees is
`Standards adopted by the technical committees are circulated to the member bodies for voting.
`Publication as an International Standard requires approval by at least 75 % of the member bodies casting
`a vote.
`
`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.
`
`ISO 5840-3 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee
`SC 2, Cardiovascular implants and extracorporeal systems.
`
`ISO 5840 consists of the following parts, under the general title Cardiovascular implants — Cardiac valve
`prostheses:
`
`— Part 3: Heart valve substitutes implanted by minimally invasive techniques
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMl/ISO 5840-3:2013
`
`ix
`
`Page 11 of 128
`
`Page 11 of 128
`
`

`

`Introduction
`
`No heart valve substitute is ideal. Therefore, a group of engineers, scientists and clinicians well aware of
`the problems associated with heart valve substitutes and their development has prepared this part of
`ISO 5840.
`In several areas, the provisions of this part of ISO 5840 have been deliberately left partially
`defined so as not to inhibit development and innovation. This part of ISO 5840 specifies types of tests,
`test methods and requirements for test apparatus. It requires documentation of test methods and results.
`This part of ISO 5840 deals with those areas that will ensure adequate mitigation of device—associated
`risks for patients and other users of the device, facilitate quality assurance, aid the cardiac surgeon and
`cardiologist
`in choosing a heart valve substitute, and ensure that the device will be presented in a
`convenient form. This part of ISO 5840 emphasizes the need to specify types of in vitro testing, preclinical
`in vivo and clinical evaluations as well as to report all in vitro, preclinical in vivo and clinical evaluations. It
`describes the labels and packaging of the device. Such a process involving in vitro, preclinical in vivo and
`clinical evaluations is intended to clarify the required procedures prior to market release and to enable
`prompt identification and management of any subsequent problems.
`
`With regard to in vitro testing and reporting, apart from basic material testing for mechanical, physical,
`chemical and biocompatibility characteristics, this part of ISO 5840 also covers important hydrodynamic
`and durability characteristics of transcatheter heart valve substitutes and their delivery systems. This part
`of ISO 5840 does not specify exact test methods for hydrodynamic and durability testing but it offers
`guidelines for the test apparatus.
`
`This part of ISO 5840 should be revised, updated and amended as knowledge and techniques in heart
`valve substitute technology improve.
`
`This part of ISO 5840 is to be used in conjunction with ISO 5840:2005, which will be replaced by
`ISO 5840—1 in future.
`
`AAMI
`Single user license provided to AAMI standards committee members.
`
`x
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMI/ISO 5840-322013
`
`Page 12 of 128
`
`Page 12 of 128
`
`

`

`
`
`
`
`American National Standard ANSIIAAMIIISO 5840-3:2013
`
`Cardiovascular implants — Cardiac valve prostheses —
`Part 3: Heart valve substitutes implanted by transcatheter
`techniques
`
`1 Scope
`
`This part of ISO 5840 outlines an approach for verifying/validating the design and manufacture of a
`transcatheter heart valve
`substitute
`through
`risk management. The
`selection of
`appropriate
`verification/validation tests and methods are to be derived from the risk assessment. The tests may
`include those to assess the physical, chemical, biological and mechanical properties of heart valve
`substitutes and of their materials and components. The tests can also include those for preclinical in vivo
`evaluation and clinical evaluation of the finished heart valve substitute.
`
`This part of ISO 5840 defines operational conditions and performance requirements for transcatheter
`heart valve substitutes where adequate scientific and/or clinical evidence exists for theirjustification.
`
`This part of ISO 5840 is applicable to all devices intended for implantation in human hearts as a
`transcatheter heart valve substitute.
`
`This part of ISO 5840 is applicable to both newly developed and modified transcatheter heart valve
`substitutes and to the accessory devices, packaging and labeling required for their implantation and for
`determining the appropriate size of heart valve substitute to be implanted.
`
`This part of ISO 5840 excludes heart valve substitutes designed for implantation in artificial hearts or
`heart assist devices.
`
`This part of ISO 5840 excludes valve-in—valve configurations and homografts.
`
`This part of ISO 5840 does not specifically address non-traditional surgically implanted heart valve
`substitutes (e.g. sutureless). For these devices, the requirements of both this part of ISO 5840 and
`ISO 5840:2005 might be relevant and can be considered.
`
`NOTE
`
`A rationale for the provisions of this part of ISO 5840 is given in Annex A.
`
`2 Normative references
`
`The following referenced documents are indispensable for the application 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—1, Biological evaluation of medical devices— Part 1: Evaluation and testing within a risk
`management process
`
`ISO 10993-2, Biological evaluation of medical devices —— Part 2: Animal welfare requirements
`
`AAMI
`Single user license provided to AAMI standards committee members
`
`© 2013 Association for the Advancement of Medical Instrumentation I ANSI/AAMI/ISO 5840—3:201 3
`
`1
`
`Page 13 of 128
`
`Page 13 of 128
`
`

`

`ISO 11135-1, Sterilization of health care products — Ethylene oxide — Part 1: Requirements for
`development, validation and routine control of a sterilization process for medical devices
`
`ISO/TS 11135-2, Sterilization of health care products— Ethylene oxide— Part 2: Guidance on the
`application of ISO 11135-1
`
`Sterilization of health care products — Radiation — Part 1: Requirements
`ISO 11137-1,
`development, validation and routine control of a sterilization process for medical devices
`
`for
`
`ISO 11137—2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization
`dose
`
`ISO 11137—3, Sterilization of health care products— Radiation— Part 3: Guidance on dosimetric
`aspects
`
`ISO 1 1607—1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
`sterile barrier systems and packaging systems
`
`ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for
`forming, sealing and assembly processes
`
`ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
`
`ISO 14160, Sterilization of health care products— Liquid chemical sterilizing agents for single-use
`medical devices utilizing animal tissues and their derivatives — Requirements for characterization,
`development, validation and routine control of a sterilization process for medical devices
`
`ISO 14630:2012, 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 22442-1, Medical devices utilizing animal tissues and their derivatives —— Part 1: Application of risk
`management
`
`ISO 22442-2, Medical devices utilizing animal tissues and their derivatives— Part 2: Controls on
`sourcing, collection and handling
`
`ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3: Validation of the
`elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
`
`ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories
`
`IEC 62366, Medical devices —— Application of usability engineering to medical devices
`
`AAMI
`Single user license provided to AAMI standards committee