`

`STENT
`6 -~ -=--=
`UPDATE
`
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`

`

`Applied Cardiovascular Medicine & Science
`Series
`
`Series Editors:
`
`Jafar Vossoughi, PhD
`Biomed Research Foundation
`Washington, DC
`
`Nicholas Kipshidze, MD, PhD
`Lenox 1/ill Heart and Vascular Institute
`Lenox Hill Hospital, New York, NY
`
`John W Karanian, PhD
`Center for Devices and Radiological Health
`US Food and Drug Administration, Rockville, MD
`
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`
`

`

`Edited by
`
`Jafar Vossoughi, PhD.
`Biomed Research Foundation
`Washington, DC
`
`Nicholas Kipshidze, MD, PhD
`Lenox Hill Hospital
`New York, NY
`
`John W Karanian, PhD·
`US Food and Drug Administration
`Rockville, MD
`
`Medical
`and
`Engineering
`Publishers, Inc
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 4 of 325
`
`

`

`©Medical and Engineering Publishers Inc 2000
`
`First published in the United States of America by
`Medical and Engineering Publishers, Inc
`PO Box 11834
`Washington, DC 20008
`USA
`(http://www.erols.com/medengrgpubinc/)
`
`All rights reserved. No part of this book may be reproduced,
`stored in any retrieval system without the prior written
`permission of the publisher.
`This
`includes copying or
`production by
`any means, mechanical, photogmphic,
`electronic, or any other means, as well as trnnslation into other
`languages.
`
`Library of Congress Cataloging-in-Publication Data
`
`Stent Graft Update
`Edited by Jafar Vossoughi, Nicholas Kipsllidze, Jo1m W
`Karanian. First edition
`Includes bibliograpllical references and index
`2000
`
`LC #: 00-107409
`ISBN#: 1-930636-00-8
`
`Copyright 2000
`Medical and Engineering Publishers, Inc
`
`Printed in tJ1e Utlited States of America.
`
`Printed on acid-free paper.
`
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`
`

`

`Contents
`
`Contents
`
`List of Contributors
`
`Acknowledgements and Disclaimer
`
`Preface
`
`Contents
`
`v
`
`v
`
`IX
`
`X Ill
`
`XV
`
`Part I: Introduction, Standards, and History
`
`1. Introductory Comments
`Elizabeth D Jacobson
`
`2. Standards for Endovascular Devices
`Dorothy B Abel
`
`3. Historical Development of Stent Grafts
`Jafar Vossoughi
`
`Part II: Biomechanics and Tissue Engineering
`
`4. Stent Graft Biomechanics
`Jafar Vossoughi
`
`5. Biomechanical and Biochemical Paths to dystrophic
`Mineralization of Stented Cardiovascular Tissues
`Jeffrey A White, Robert E Baier, Anne E Meyers,
`Redmond P Burke, Ernest M Hausmann
`
`6. Accelerated Test Criteria for Stented Grafts
`Narendra K Simha, Ned H C Hwang
`
`7. Tissue Engineered Vascular Grafts
`LeeK Landeen, Joan Zeilinger, Ann A Lee, Holly G Alexander,
`Dionne A Graham, Michael R Fino, Anthony Ratcliffe,
`Gail K Naughton
`
`3
`
`7
`
`15
`
`25
`
`37
`
`67
`
`89
`
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`

`

`v1 Contents
`
`Part III: Biologic Response
`
`8. Laser Scanning Confocal Fluorescence Microscopy:
`An Emerging Technique for the Pathologic Evaluation of
`Cardiovascular Devices
`Stephen L Hilbert, Du-Xi Yu, Steven Archuleta, Victor J Ferrans
`
`115
`
`9. Thrombosis and Thromboembolism in Stent Grafts :
`Evaluating Virchow's Triad
`William R Wagner, Kenneth L Gage
`
`10. A Pathologist's View of Stenting: Bare Stents and
`Stent Grafts
`Andrew Farb, Frank D Kolodgie, Renu Virmani
`
`Part IV: Animal Modeling
`
`11. From Concept to Operating Room: Role ofthe FDA in the
`Development of Stent Grafts
`John W Karanian
`
`12. A Critical .Overview of Animal Models for
`Stent Graft Research
`Michael J Hallisey, Kenneth Wright
`
`125
`
`141
`
`169
`
`177
`
`13. Stent and Stent Graft Modeling in the Canine
`David L Gillespie, Lois A Fiala, Frank Kolodgie, Renu Vermani,
`Ray Workmam, Neal Hadro
`
`185
`
`14. Large animal Models in Pre-Clinical Trials
`Diane Wray-Cahen, Jajar Vossoughi, John W Karanian
`
`15. Industrial Perspectives on Animal Modeling for
`Stent Graft Evaluation
`Thomas McCarthy
`
`16. Stent Grafts: From Animal Models to Human
`Clinical Applications
`Anthony C Venbrux
`
`201
`
`215
`
`223
`
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`

`

`Part V: Clinical Perspectives
`
`17. Montefiore Experience with Endovascular Grafts
`for the Treatment of Aneurysms and other Arterial
`Lesions: A Five Year Experience
`Takao Ohki, Frank J Veith
`
`18. Experimental and Clinical Development of Aortic
`Stent Grafts and Review of Contemporary
`Types of Devices
`Nicholas Kipshidze, Harry Sahota, Ivan Bakhutashvili
`
`19. Endovascular Aortic Grafting- Investigator's
`Experience from Laboratory Concept to Clinical Trial
`Rodney A White, Carlos Donayre, Irwin Walot,
`George E Kopchok
`
`Subject Index
`
`Contents vu
`
`233
`
`269
`
`287
`
`301
`
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`

`

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`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 9 of 325
`
`

`

`List of Contributors
`
`Dorothy BAbel
`Office of Device Evaluation and
`Radiological Health
`Food and Drug Administration
`9200 Corporate Blvd
`Rockville, MD 20850
`
`Holly G Alexander, BA
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
`Steven Archuleta, BA
`Center for Devices and
`Radiological Health
`Food and Drug Administration
`12725 Twinbrook Parkway
`Rockville, MD 20852
`
`Robert E Bair, PhD, PE
`NSF Industry/University
`Cooperative Research Center
`for Biosurfaces
`State University ofNew York at
`Buffalo
`110 Parker Hall
`Buffalo, NY 14214-3007
`
`Ivan Bakhutashuili, MD, PhD
`Medical College ofWisconsin
`9200 West Wisconsin Ave.
`Milwaukee, WI 53226
`
`Redmond P Burke, MD
`Division of Cardiovascular
`Surgery
`Miami Children•s Hospital
`33200 SW 60 Court, Suite 102
`Miami, FL 33155-4069
`
`Contributors
`
`ix
`
`Carlos Donayre, MD
`Division of Vascular Surgery
`Harbor-UCLA Medical Center
`1 000 West Carson Street
`Torrance, CA 90509
`
`Andrew Farb, MD
`Department of Cardiovascular
`Pathology
`Armed Forces Institute of
`Pathology
`Washington, DC 20306-6000
`
`Victor J Ferrans, MD, PhD
`Pathology Section
`National Heart, Lung and Blood
`Institute
`National Institutes of Health
`Bethesda, MD 20205
`
`Lois A Fiala, MD
`Department of Surgery
`Uniformed Services University
`of the Health Services
`4301 Jones Bridge Road
`Bethesda, MD 20814
`
`Michael R Fino, BS
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
`Kenneth L Gage
`University of Pittsburgh
`Center for Biotechnology and
`Bioengineering
`Room 407
`300 Technology Drive
`Pittsburgh, PA 15219
`
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`
`

`

`x Contributors
`
`David Gillespie, MD
`Department of Surgery
`Uniformed Services University
`of the Health Services
`4301 Jones Bridge Road
`Bethesda, MD 20814
`
`Dionne A Graham, MS
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
`Neal Hadro, MD
`Department of Surgery
`Uniformed Services University
`of the Health Services
`4301 Jones Bridge Road
`Bethesda, MD 20814
`
`Michael Hallisey, MD
`Connecticut Vascular Institute
`University of Connecticut
`School of Medicine, Suite 911
`85 Seymour Street
`Hartford, CT 06106
`
`EM Hausmann, DMD, PhD
`School of Dental Medicine
`State University ofNew York at
`Buffalo
`Department of Oral Biology
`365 Squire Hall
`Buffalo, NY 14214-3008
`
`Stephen L Hilbert, MD, PhD
`Center for Devices and
`Radiological Health
`Food and Drug Administration
`12725 Twinbrook Parkway
`Rockville, MD 20852
`
`Ned H C Hwang, PhD
`Medical Engineering Division
`National Health Research Inst
`128 Yen-Chiu-Yea Road
`Taipei 11529, Taiwan, ROC
`
`Elizabeth D Jacobson, PhD
`Deputy Director for Science
`Office of the Commissioner
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20852
`
`John W Karanian, PhD
`Office of Device Evaluation and
`Laboratory of Large Animal
`Research
`Center for Devices and
`Radiological Health
`Food and Drug Administration
`Rockville, MD 20850
`
`Nicholas Kipshidze, MD, PhD
`Lenox Hill Heart and Vascular
`Institute
`Lenox Hill Hospital
`130 East 77th Street
`New York, NY 10021
`
`Frank Kolodgie, MD
`Department of Cardiovascular
`Pathology
`Armed Forces lnst of Pathology
`Washington, DC 20306-6000
`
`George E Kopchok, BS
`Division of Vascular Surgery
`Harbor-UCLA Medical Center
`1000 West Carson Street
`Torrance, CA 90509
`
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`
`

`

`Lee K Landeen, MS
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
`Ann A Lee, PhD
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 9203 7
`
`Anne E Myer, PhD
`NSF Industry/University
`Cooperative Research Center
`for Biosurfaces
`State University ofNew York at
`Buffalo
`110 Parker Hall
`Buffalo, NY 14214-3007
`
`Thomas J McCarthy, DVM
`Baxter Healthcare Corporation
`17221 Red Hill Ave, MIS 44
`Irvine, CA 92614
`
`Gail K Naughton, PhD
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
`Takao Ohki, MD
`Division of Vascular Surgery
`Albert Einstein College of
`Medicine
`Montefiore Medical Center
`111 East 21 Oth Street
`New York, NY 10467
`
`Anthony Ratcliffe, PhD
`Advanced Tissue Sciences, Inc
`10933 North Tarrey Pines Road
`La Jolla, CA 92037
`
`Contributors
`
`xi
`
`Narendra K Simha, PhD
`Department of Mechanical
`Engineering
`PO Box 248294
`University of Miami
`Coral Gables, FL 33124
`
`Harry Sahota, MD
`Good Samaritan Hospital
`9810 Park Street
`Bellflower, CA 90706
`
`Frank J Veith, MD
`Division of Vascular Surgery
`Albert Einstein College of
`Medicine
`Montefiore Medical Center
`lll East 21 Oth Street
`New York, NY 10467
`
`Anthony C Venbrux, MD
`Radiology and Surgery
`Cardiovascular and
`International Radiology Lab
`The Johns Hopkins Medical
`Institutions
`600 N Wolfe St, Blalock 544
`Baltimore, MD 2 I 2 8 7
`
`Renu Virmani, MD
`Department of Cardiovascular
`Pathology
`Armed Forces Institute of
`Pathology
`Washington, DC 20306-6000
`
`Jafar Vossoughi, PhD
`Biomed Research Foundation
`440 1-A Connecticut Ave, NW
`PMB 327
`Washington, DC 20008-2322
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 12 of 325
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`

`

`xu Contributors
`
`William R Wagner, PhD
`University of Pittsburgh
`Center for Biotechnology and
`Bioengineering
`Room 407
`300 Technology Drive
`Pittsburgh, PA 15219
`
`Irwin W alot, MD
`Division of Radiology
`Harbor-UCLA Medical Center
`1000 West Carson Street
`Torrance, CA 90509
`
`Jeffrey A White, MS
`Division of Cardiovascular
`Surgery
`Miami Children's Hospital
`33200 SW 60 Court, Suite 102
`Miami, FL 33155-4069
`
`Rodney A White, MD
`Division of Vascular Surgery
`Harbor-UCLA Medical Center
`l 000 West Carson Street
`Torrance, CA 90509
`
`Ray Workman, MD
`Department of Surgery
`Uniformed Services University
`of the Health Services
`4301 Jones Bridge Road
`Bethesda, MD 20814
`
`Diane Wray-Cahen, PhD
`Center for Devices and
`Radiological Health
`FDA, OST DLS/ HSB
`Laboratory of Large Animal
`Research
`8401 Muirkirk Road
`Laurel, MD 20708
`
`Kenneth Wrigh, PhD
`Department of Diagnostic
`Radiology-05 7
`University of Texas
`MD Anderson Cancer Center
`1515 Holcon1be Blvd
`Houston, TX 77030
`
`Zu-Xi Yu, MD, PhD
`Center for Devices and
`Radiological Health
`Food and Drug Administration
`12725 Twinbrook Parkway
`Rockville, MD 20852
`
`Joan Zeltinger, PhD
`Advanced Tissue Sciences, Inc
`10933 North Torrey Pines Road
`La Jolla, CA 92037
`
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`

`

`Xlll
`
`ACKNOWLEDGEMENTS
`
`We are pleased to acknowledge the excellent contributions of the authors
`of the chapters. Eclitorial assistance of Theresa Conway~ Daniel Shimko,
`and Elizabeth Browning is greatly acknowledged.
`
`We are also grateful to the FDA Center for Veterinary Medicinet
`Office of Research for providing meeting space for the Workshop; This
`book was generated from the lectures given at the Stent Graft Workshop
`took place at the FDA - CVM.
`
`Without our industrial sponsors, the Workshop and this book could not
`have been possible. The editors and the authors are, therefore, indebted
`to:
`
`Advanced Tissue Sciences, Inc
`Baxter Healthcare Corporation
`Bio-Vascular, Inc
`Boston Scientific Corporation
`WL Gore & Associates
`
`DISCLAIMER
`
`The opinions presented in this book are the opinions of the individual
`authors and are not to be construed as conveying either an official
`endorsement or criticism by any of the editors and the industrial sponsors
`including the US Department of Health and Human Services and the
`Food and Drug Administration.
`
`Every effort has been made to ensure the accuracy of the information
`presented in this book. However, due to the constant and rapid
`development in medical technology, editors, authors, nor the publisher
`can accept any legal or other responsibilities for the errors, accuracy and
`omissions that may have occurred at the time of publication.
`
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`

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`

`

`Preface
`
`xv
`
`PREFACE
`
`This book is the first in a series of books and monographs planned to be
`published in the general area of "Applied Cardiovascular Medicine and
`Science."
`
`The book contains chapters that are based on talks given at the "Stent
`Graft Workshop" held recently at the FDA - Center for Veterinary
`Medicine, Laurel, Maryland. The workshop was organized by the three
`editors
`and
`its purpose was
`to bring
`together professional,
`manufacturing, and
`regulatory communities
`to discuss
`the
`latest
`developments related to stent grafts. In particular, the objectives of the
`meeting were to: 1) foster communication between the professional,
`regulatory communities; and 2) generate a
`manufacturing, and
`preclinicaUclinical stent graft update which summarizes current device
`safety and performance.
`
`J afar Vossoughi
`vossoughi@msn.com
`Nicholas Kipshidze
`nkipshdze@compuserve.com
`John W Karanian
`Jwk@cdrh.fda.gov
`
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`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 17 of 325
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`

`

`Part I
`
`INTRODUCTION, STANDARDS, AND
`·:HISTORY
`
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`

`

`Chapter 1
`
`INTRODUCTORY COMMENTS
`
`Elizabeth D Jacobson, PhD
`
`Greetings on behalf of the FDA's Center for Devices and Radiological
`Health (CDRH). The contributions to this workshop on stent grafts are
`outstanding and represent both the preclinical and clinical cutting edge in
`this area of research. Since I do not want to take too much time from the
`program, my introductory comments will be brief.
`
`There is great interest in this topic, given the significance of the
`therapeutic values of these devices. One of the concerns that both FDA
`and its critics have, when faced with a fast-moving technology, is that
`FDA will end up being a bottleneck as companies submit premarket
`approval applications for products. There are at least three ways to
`vaccinate against this:
`
`• By early, vigorous and open discussions of the scientific and
`.
`.
`.
`engmeenng tssues,
`• By early consultation between FDA and industry when a product is
`envisioned,
`• By the use of consensus standards whenever possible.
`
`Elizabeth Jacobson, PhD (corresponding author), Deputy Director for
`Science, Office of the Commissioner, Food and Drug Administration,
`5600 Fishers Lane, Rockville, MD 20852
`Stent Graft Update, Edited by J Vossoughi, N Kipshidze, JW Karanian
`©2000 Medical and Engineering Publishers, Inc
`(http://www.erols.com/medengrgpubinc/)
`
`3
`
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`

`

`4 E DJacobson
`
`The need for open scientific discussion is obviously bringing coals to
`Newcastle for this group. We need critical dialogue leading to both a
`clear understanding of the critical scientific issues and of the critical
`questions needing resolution for premarket applications.
`
`the professional,
`take place between
`should
`This dialogue
`regulatory communities. Early discussion and
`manufacturer and
`agreement on what is scientifically necessary save false steps. Dialogue
`needs to happen at the earliest stages of product development and
`continue through the developmental lifetime of the product. We at the
`agency are committed to early and rapid decisions. A few years ago, 75%
`of applications for Investigational Device Exemptions (IDE's) were
`turned down on the first round. Today, 75% are accepted. This was not
`by accident. The Center has worked hard to get questions resolved early
`through discussions with sponsors. Further, Congress has codified in the
`newest FDA law, the Food and Drug Administration Modernization Act
`of 1997 (FDAMA), the need for pre-IDE discussions.
`
`We really did not need Congress to tell us that this was a good idea, we
`were already doing it. Moving prevalent technology, such as stent grafts,
`safely and expeditiously through preclinical and clinical trials is a good
`example ofthe system working.
`
`The proceedings of this Stent Grafts Workshop will be an excellent
`representation of the current status of this technology. This publication
`will serve as a touchstone for current information on the safety and
`effectiveness of these devices.
`
`I know that our professional and industry colleagues would like to
`obtain information itemizing what needs to get done to obtain quick
`approval, and probably are justifiably dissatisfied with the lack of
`guidance in this area.
`
`However, when a field is moving rapidly, it is difficult to generate
`good guidance. We hope the proceedings from this workshop can assist
`in this regard and serve as the basis for guidance and for consensus
`standards.
`
`As some of you may know, FDAMA has given us the ability to
`recognize consensus standards in order to streamline the review process.
`To date, we have recognized nearly 400 standards and are very interested
`
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`
`

`

`Introductory Comments 5
`
`those
`to
`rece1v1ng manufacturer declarations of confonnance
`in
`standards. When such a declaration is made, manufacturers do not need
`to submit the data showing confonnance to the agency, but need only
`keep it on fi I e. This makes for a Jess bulky application and more
`expedient review time -- something to keep in mind for stent grafts.
`These proceedings also address the details of stent graft standards
`development to date.
`
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`

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`

`

`Chapter 2
`
`STANDARDS FOR ENDOV ASCULAR
`DEVICES
`
`Dorothy B Abel
`
`Standards for medical devices are intended to promote consistent and
`comprehensive evaluations of the devices within the scope of the
`standard. Webster defines a standard as "an accepted measure of
`comparison for quantitative or qualitative value: Criterion." For medical
`devices, this generally translates into the compilation and recognition of
`accepted requirements and methods.
`
`endovascular grafts, pose
`particularly
`Endovascular devices,
`difficulties in writing standards because the requirements and testing
`methods have not yet been established for these devices. This is
`primarily due to the novelty and diversity of this product area with
`respect to both the device designs and their clinical application. These
`limitations have not only affected the development of standards, but also
`restricted the scope of workshops and seminars devoted to these
`
`Keywords: Standards, medical devices, endovascular devices, ISO
`initiatives, Association for the Advancement of Medica/Instrumentation
`
`Dorothy BAbel (corresponding author), Office of Device Evaluation and
`Radiological Health, US Food and Drug Administration (HFZ-450),
`9200 Corporate Blvd, Rockville, MD 20850.
`The views and opinions expressed here are those of the author and do not
`necessarily reflect those of the US Food and Drug administration, US
`Department of Health and Human Services, and the Public Health Service.
`Stent Graft Update, Edited by J Vossoughi, N Kipshidze, JW Karanian
`©2000 Medical and Engineering Publishers, Inc
`(http://www.erols.com/medengrgpubinc/)
`
`7
`
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`

`

`8 DBAbel
`
`the
`Such meetings are certainly valuable, however,
`products.
`information presented should be considered within the context of the
`mature of the technology. Although useful insight is provided by experts
`in the various means of interest, it is important to keep in mind that
`consensus has not yet been achieved.
`In addition, with respect to
`endovascular grafts, the Food and Drug Administration (FDA) has not
`specified, nor recognized, any specific testing requirements.
`
`ISO INITIATIVES FOR ENDOVASCULAR DEVICES
`
`The vascular prostheses working group of the International Organization
`of Standardization
`(ISO)
`is working on
`the standardization of
`endovascular devices. The group had intended to work on developing
`standards for endovascular grafts. The work was expanded to cover
`endovascular devices, as members of the committee who also participate
`in the ongoing efforts of the European Community lobbied to expand the
`scope to be consistent with their projects. As a result, the ISO committee
`is now responsible for standardizing endovascular grafts, bare stents,
`vena cava filters, venous stents and TIPS stents. The delivery systems
`for these devices are also currently being included in this work item.
`
`As it is premature to write a standard for these devices, the committee
`decided to write a technical report first1
`• A Technical Report type 2
`format was chosen due to the fact hat these endovascular devices are still
`under technical development. With the relatively recent development of
`some of these devices, acceptable standardized in vitro tests and long
`term results of clinical trials are not yet available. This technical report
`aims to insure that manufacturers will address all aspects of design
`evaluation that relate to the safety of the product. This report will
`essentially become the rationale for the requirements that will be
`included in a future standard(s) for these devices. It will also be valuable
`in standardizing the terminology for these devices. Since this is a unique
`approach toward developing a standard, the contents of the report are
`described.
`
`The critical components of the technical report are found in the
`Annexes. Annex A of the ISO technical report contains a table intended
`to provide a logical method for identifying a set of tests to assess
`endovascular device performance. This table is titled the "Attributes
`Table." Annex B includes a Jist of the Bench Tests identified in the
`Attributes Table, with a description for the purpose of each test, and
`
`1 Committee draft ISO/CD ISO/DTR 15539-1998
`
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`

`

`Standards for Endovascu/ar Devices
`
`9
`
`Annex C includes definitions for the Reportable Accessory Devices, and
`Annex E contains a bibliography.
`
`Table 1 explains the headings for the Attributes Table.
`information is included in the introduction to Annex A of the report.
`
`This
`
`Column
`Number
`1
`
`2
`
`3
`
`4
`
`5
`
`f
`
`TABLE 1
`EXPLANATION OF ATTRIBUTES TABLE
`Title
`Explanation
`Context
`
`Individual
`design goals
`
`The device should have an
`adequate __ (Column 1 ).
`
`If the device does not have
`an adequate _(Column 1),
`there could be a problem
`with
`(Column 2).
`
`I
`
`Device/
`Procedure
`Related
`Attributes
`Problem(s) Difficu I ties that
`may be
`encountered that
`could resu It in
`not meeting the
`individual
`design goal.
`' Reportable Complications
`If there is a problem with
`(Column 2), _(Column 3)
`Clinical
`or failures that
`Events
`may be observed could occur and should be
`with clinical use
`documented.
`if the problems
`occur.
`A list of tests,
`The following tests may
`exclusive of
`be conducted to evaluate
`animal and
`the adequacy of the
`clinical studies, __ (Column 1):
`__ (Column 4).
`that may be
`conducted to
`validate and
`verify the
`individual
`design goal.
`Specified aims
`of animal
`studies to vali-
`date and verify
`the individual
`design goal
`
`Bench
`Tests
`
`Animal
`Studies
`
`In order to evaluate the
`adequacy of the
`_Column 1) an in vivo
`environment, the animal
`study should _(Coh.1mn 5)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 26 of 325
`
`

`

`10 DBAbel
`
`6
`
`7
`
`Clinical
`Studies
`
`Information
`Supplied by
`the
`Manufacturer
`
`TABLE 1
`
`CONTINUED
`In order to evaluate the
`Specific aims
`adequacy of the _
`of clinical
`(column 1) in a clinical
`studies to
`environment, the clinical
`verify the
`study should _(Column
`individual
`6)
`design goal
`Information to To minimize the risk of -
`be supplied by
`(Column 2) or_
`(Column 3), _(Column 7)
`the manu·
`facturer to
`should be provided by the
`manufacturer.
`minimize the
`potential for
`failures to
`occur
`
`The exercise of completing the rows of the Attributes Tables was done
`for about 20 attributes for the delivery system and implant, with
`understandably fewer attributes
`for
`the accessory devices.
`By
`systematically identifying the design goals, the potential problems that
`could be encountered, and the clinical events, appropriate tests and
`information that need to be supplied by the manufacturer were identified.
`
`An example of a row in the Attributes Table in Annex A, for the
`attribute fixation effectiveness follows:
`
`The problems that could be encountered if there is not adequate fixation
`effectiveness include incomplete apposition to the vessel wall and
`excessive or inadequate radial force . These problems could lead to a list
`of clinical events, such as attachment site leak and prosthesis migration.
`The list of bench tests, such as radial force and crush resistance, may be
`conducted to evaluate the adequacy of the fixation effectiveness for the
`device. The specific aims of the animal studies to evaluate the adequacy
`of the fixation effectiveness should include: to assess position, integrity
`and functionality, to conduct appropriate histological and pathological
`investigation of explants, and to evaluate the previously identified
`reportable clinical events. The specific aims of the clinical studies to
`evaluate the adequacy of the fixation effectiveness should be the same as
`those for the animal studies, with the addition of the aim to monitor
`lesion morphology. The information to be supplied by the manufacturer
`should include directions regarding restrictions and requirements to
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 27 of 325
`
`

`

`Standards for Endovascular Devices
`
`11
`
`assure proper fixation, for example anatomical restrictions and sizing
`recommendations. This example is presented here in columnar form.
`
`TABLE2
`
`EXCERPT FROM ATTRIBUTE TABLE
`
`Device/Procedure Related
`Attributes
`Problem(s)
`
`Reportable Clinical Events
`
`Bench Tests
`
`Animal Studies
`
`Clinical Studies
`
`Fixation Effectiveness
`
`-Incomplete apposition to vessel wall
`-Excessive or inadequate radial force
`-Attachment site leak
`-Prosthesis migration
`-Lumen obstruction
`-Vascular trauma
`-Trauma to adjacent structures
`-Branch vessel Occlusion
`-Aneurysm enlargement
`-Aneurysm rupture
`-Radial force
`-Crush resistance
`-Recoil
`-Local Compression
`-Conformability to vessel wall
`-Migration Resistance
`-Simulated use
`-Assess position, integrity and
`functionality
`-Appropriate histological and
`pathological investigation of explants
`-Evaluate reportable clinical events
`-Assess position, integrity and
`functionality
`-Monitor lesion morphology
`-Appropriate histological and patho-
`logical investigation of explants
`-Evaluate reportable clinical events
`N/A
`
`Information Supplied by the
`Manufacturer
`The applicable rows from the table in Annex B that explain the purpose
`of each listed bench test are as follows:
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 28 of 325
`
`

`

`12 DBAbel
`
`TABLE 3
`
`EXCERPT FROM BENCH TESTS TABLE
`
`Confonnability to Vessel Evaluate device conformity to vessel wall.
`Wall
`Crush Resistance
`
`Local Compression
`
`Migration Resistance
`
`Radial Force
`(Hoop Strength)
`
`, Recoil
`
`Simulated Use
`
`Record the minimum force at which
`pennanent deformation occurs.
`Evaluate the elastic deformation of the device
`in response to localized pressure.
`Ability of device to remain stationary under
`simulated use.
`Evaluate the change in diameter of a self-
`expanding device as a function of radially
`applied pressure.
`Quantify the amount of elastic recoil and
`correlate this to recommended sizing. This
`information should be made available by the
`manufacturer.
`A model, which simulates the intended use of
`conditions and allows the evaluation ofthe
`a_p_plicable performance parameters
`
`'
`
`Finally, the applicable rows from the Table in Annex C which define the
`reportable clinical events are as follows:
`
`TABLE 4
`
`EXCERPT FROM REPORTABLE EVENTS TABLE
`
`Aneurysm
`Enlargement
`
`Aneurysm
`Rupture
`Attachment
`Site Leak
`
`Any enlargement of the diameter or volume of the
`aneurysm sac greater than documented measurement
`error, as determined by contrast enhanced CT or other
`ap_Qropriate modality
`The rupture of the native aneurysm sac
`
`Blood flow into the aneurysm sac arising at or from the
`attachment site occurring at any time after endovascular
`repair as determined by contrast CT scan, ultrasound,
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 29 of 325
`
`

`

`Branch Vessel
`Occlusion
`Lumen Obstruction
`
`Prosthesis Migration
`
`Trauma to Adjacent
`Structures
`Vascular Trauma
`
`Standards for Endovascular Devices
`
`13
`
`TABLE4
`
`CONTINUED
`angiography or direct observation at surgery or
`autopsy
`Clinically significant, unplanned exclusion of a
`major branch vessel
`Unintentional obstruction of flow through the
`vascular lumen due to twisting or kinking of
`the prosthesis, oversizing, failure of the device
`to fu11y open, or any other cause
`Longitudinal movement of all or part of a stent
`or attachment system for a distance of greater
`than 1 em relative to anatomical landmarks
`determined prior to discharge
`Injury to adjacent structures associated with
`vascular trauma (see definition below)
`Injuries to vessels as a result of an
`endovascular procedure, including dissections
`or perforations. The specific site and source of
`the injury as well as the clinical sequelae
`should be reported. All required surgical or
`interventional procedures required to repair the
`injury should also be reported.
`
`This example demonstrates the logic used to develop the ISO report
`and the level of information captured in the report. Clearly this report
`cannot be used as a laundry list for testing to be completed on an
`endovascular device, but rather, may be used as a template in completing
`the exercise of identifying the appropriate testing for each individual
`device.
`
`STATUS AND SUMMARY
`
`The Technical Report was distributed to the member countries of ISO for
`comment and these comments were discussed at a meeting in London in
`October. After resolving the comments, the document will be modified
`as appropriate and distributed for comment and vote. Hopefully, the
`report will be published within a year.
`
`This report, particularly the Attributes Tables, will form the basis for
`the requirements of a future standard for these devices. The strategy for
`developing the standard (eg, whether to do separate parts or combine all
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 30 of 325
`
`

`

`14 D BAbel
`
`devices) will need to be discussed at future meetings of the working
`group.
`
`this effort should call Joe
`Anyone interested in participating in
`L~welling of the Association for
`the Advancement of Medical
`Instrumentation (AAMI), the secretariat to ISO for this committee, at
`(703) 525-4890, extension 206.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1041, p. 31 of 325
`
`

`

`Chapter 3
`
`HISTORICAL DEVELOPMENT OF STENT
`GRAFTS
`
`Jafar Vossoughi, PhD
`
`Stent grafts are used for the endovascular treatment of abdominal aortic
`aneurysms (AAA), arteriovenous fistulas (A VF), arterial false aneurysms
`the
`thoracic
`treatment of dissecting aneurysms (DA), and