PROCEEDINGS FROM THE WORKSHOP ON SCIENCE-BASED ASSESSMENT
ACCELERATING PRODUCT DEVELOPMENT OF COMBINATION MEDICAL DEVICES
Bonnie A. Scarborough, Editor
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.
Support for this project was provided by Alfred University, Boston Scientific Corporation, California State University Program for Education and Research in Biotechnology, Center for Integration of Medicine and Innovative Technology, Dow Chemical Company, Edwards Lifesciences Corporation, Johnson & Johnson, Medtronic, Inc., National Institute of Standards and Technology, National Institutes of Health, National Science Foundation, New Jersey Associated Institutions for Materials Science, Office of Naval Research, University of Florida, U.S. Army, U.S. Department of Veterans Affairs, and U.S. Food and Drug Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.
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Copyright 2004 by the National Academy of Sciences. All rights reserved.
Case cover images (left to right):
Absorbable collagen sponge carrier and LT-CAGETM lumbar tapered fusion device; images courtesy of W. McKay, Medtronic Sofamor Danek.
TransluteTM carrier; courtesy of R. Sahatjian, Boston Scientific Corporation.
Cartilage-bone construct grown in vitro; courtesy of A. Ratcliffe, Synthasome, Inc.
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THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.
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ROUNDTABLE ON BIOMEDICAL ENGINEERING MATERIALS AND APPLICATIONS
ROBERT M. NEREM, Chair,
Georgia Institute of Technology, Atlanta
MINDY AISEN,
U.S. Department of Veterans Affairs, Washington, D.C.
PAUL CITRON,
Medtronic, Inc., Minneapolis, Minnesota
CRYSTAL CUNANAN,
Edwards Lifesciences Corporation, Irvine, California
A. STEPHEN DAHMS,
California State University Program for Education and Research in Biotechnology, San Diego
ALAN GOLDSTEIN,
Alfred University, Alfred, New York
SUZANNE JANICKI,
The Dow Chemical Company, Midland, Michigan
CAROL LUCAS,
National Science Foundation, Arlington, Virginia
WINFRED PHILLIPS,
University of Florida, Gainesville
THOMAS REID,
Walter Reed Army Institute of Research, Silver Spring, Maryland
DIANNE REKOW,
New York University, New York
JONATHAN JAY ROSEN,
Center for Integration of Medicine and Innovative Technology, Boston, Massachusetts
RONALD SAHATJIAN,
Boston Scientific Corporation, Natick, Massachusetts
JOEL M. SCHNUR,
Naval Research Laboratory, Washington, D.C.
ANGELO SCOPELIANOS,
Johnson & Johnson, Somerville, New Jersey
RICHARD E. SWAJA,
National Institute of Biomedical Imaging and Bioengineering, Bethesda, Maryland
JOHN A. TESK,
National Institute of Standards and Technology, Gaithersburg, Maryland
TERRY O. WOODS,
U.S. Food and Drug Administration, Rockville, Maryland
NRC Staff
BONNIE A. SCARBOROUGH, Program Officer
TERI THOROWGOOD, Research Associate
EMILY ANN MEYER, Research Associate
MARTA VORNBROCK, Research Assistant
LAURA TOTH, Project Assistant
PABLO WHALEY, Intern
NATIONAL MATERIALS ADVISORY BOARD
JULIA M. PHILLIPS, Chair,
Sandia National Laboratories, Albuquerque, New Mexico
JOHN ALLISON,
Ford Motor Company, Dearborn, Michigan
PAUL BECHER,
Oak Ridge National Laboratory, Oak Ridge, Tennessee
BARBARA D. BOYAN,
Georgia Institute of Technology, Atlanta
ROBERT J. CAVA,
Princeton University, Princeton, New Jersey
DIANNE CHONG,
The Boeing Company, St. Louis, Missouri
FIONA DOYLE,
University of California, Berkeley
GARY FISCHMAN, Consultant,
Palatine, Illinois
KATHERINE G. FRASE,
IBM, Hopewell Junction, New York
HAMISH L. FRASER,
Ohio State University, Columbus
JOHN J. GASSNER,
U.S. Army Natick Soldier Center, Natick, Massachusetts
THOMAS S. HARTWICK,
TRW, Redmond, Washington
ARTHUR H. HEUER,
Case Western Reserve University, Cleveland, Ohio
ELIZABETH HOLM,
Sandia National Laboratories, Albuquerque, New Mexico
FRANK E. KARASZ,
University of Massachusetts, Amherst
SHEILA F. KIA,
General Motors Research and Development Center, Warren, Michigan
CONILEE G. KIRKPATRICK,
HRL Laboratories, Malibu, California
ENRIQUE J. LAVERNIA,
University of California, Davis
TERRY LOWE,
Los Alamos National Laboratories, Los Alamos, New Mexico
HENRY J. RACK,
Clemson University, Clemson, South Carolina
LINDA SCHADLER,
Rensselaer Polytechnic Institute, Troy, New York
JAMES C. SEFERIS,
University of Washington, Seattle
T.S. SUDARSHAN,
Materials Modification, Inc., Fairfax, Virginia
JULIA WEERTMAN,
Northwestern University, Evanston, Illinois
NRC Staff
TONI MARECHAUX, Director
Preface
INTRODUCTION
The Food, Drug, and Cosmetics Act of 1938 and the Safe Medical Devices Act of 1990 have driven the development of much of the current science for assessing materials, devices, drugs, and biologics. The U.S. Food and Drug Administration (FDA) has established testing centers that specialize in the assessment of products belonging to one of three categories:
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Device: an apparatus or implant, including any component or accessory, intended for the diagnosis, mitigation, treatment, or prevention of disease or intended to affect the structure or function of the body, that does not achieve its primary intended purposes through chemical action within or on the body and that is not dependent on being metabolized;
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Biologic: a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine applicable to the prevention, treatment, or cure of a disease; and
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Drug: (a) an article recognized in the official United States Pharmacopoeia, official Homeopathic Pharmacopoeia of the United States, or official National Formulary, (b) an article intended for the prevention, diagnosis, treatment, or cure of a disease, or (c) an article other than food intended to affect the structure or any function of the body.
New patient therapies are becoming more complex, however. The FDA is just now beginning to deal with the issue of how to evaluate “combination products,” that is, products that are made up of components from more than one of these categories. Timely assessment of these devices is important from both a public health and an economic standpoint. The safe and effective development of such combination products requires an understanding of their failure mechanisms as well as an assessment of the risk associated with failure. Currently, devices, biologics, and drugs are all evaluated using different review standards. But for certain combination products, especially breakthrough products, it may not be clear which review standard(s) should apply. In addition, in some cases, scientific methodologies to appropriately assess some combination products may not yet exist or be fully developed, although the therapeutic endpoints for many of these products exist and are well understood (e.g., drug-eluting stents). Combination products thus pose new challenges with respect to the assessment of efficacy and safety. It is important to determine the extent, if any, to which differences in the testing
of combination products may create barriers to innovation or delays in bringing products to those in need.
ROUNDTABLE ON BIOMEDICAL ENGINEERING MATERIALS AND APPLICATIONS
The Roundtable on Biomedical Engineering Materials and Applications (BEMA) is an activity of the National Research Council (NRC) convened with the objective of bringing together government officials, industry representatives, academics, and others to discuss research, development, applications, and regulation of biomedical materials and devices. BEMA provides a forum for participants to identify opportunities for applying engineering principles to create and improve the clinical performance of medically useful materials and devices. In addition, the roundtable discusses strategies for overcoming the technical, legal, and cultural obstacles that impede the transition of new materials and devices into clinical application. BEMA achieves these objectives by:
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Providing a neutral setting for the exchange of information about issues related to biomaterials science, research, and practice;
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Identifying and discussing priority issues in the general area of biomaterials and their application in the development, manufacture, and use of medical devices; and
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Conducting problem-solving and issue-identification activities such as workshops that address these issues in greater depth.
WORKSHOP ON SCIENCE-BASED ASSESSMENT
A workshop entitled “Science-Based Assessment: Accelerating Product Development of Combination Medical Devices” was held on April 22-23, 2003, at the National Academies in Washington, D.C. (the theme was identified in BEMA meetings held the previous year). The purpose of the workshop was to discuss science-based assessment that can be used to effectively evaluate biomedical materials and combination devices. To facilitate discussion, the workshop was organized into sessions on three specific types of combination products: orthopedic repair using bone morphogenetic protein; drug-eluting stents; and cell-matrix cartilage implants. Abstracts of the presentations in each of these sessions are included in this report, as are abstracts of overarching, context-setting discussions of science-based assessment and experimental design. The agenda for the workshop is included in Appendix A and biographical sketches of the speakers are given in Appendix B. The viewgraphs presented by the speakers are reproduced, as originally supplied, on the attached CD-ROM.
NRC roundtables are established solely to provide open forums for discussion of emerging issues. They are prohibited by NRC policy from producing conclusions and recommendations or from offering advice to government agencies. As such, the primary purpose of this workshop was to educate the individuals who attended so that they might take this information back to their organizations and use it in their daily planning and decision making. This proceedings therefore serves primarily as a guide to those participants in remembering the content of the discussions. The abstracts of the workshop presentations and the unedited viewgraphs represent solely the viewpoints of the presenters.
ACKNOWLEDGMENTS
On behalf of BEMA, I would like to thank the speakers, session chairs, panelists, and attendees who participated in the workshop. The strong presence from government, industry, and academia was responsible for the success of the event and the lively discussions that took place. I would also like to thank those BEMA members who worked hard to organize this workshop and who, by their tireless efforts, brought the right people to the right place at the right time. Finally, I would like to thank the NRC staff members who were instrumental in organizing the workshop and preparing this report: Bonnie Scarborough, Toni Maréchaux, Teri Thorowgood, Emily Ann Meyer, Marta Vornbrock, Laura Toth, and Pablo Whaley.
Thanks are also extended to the following individuals, who reviewed the contents of this proceedings volume: Tara Federici, AdvaMed; Jean Jacob, Louisiana State University; John Ranieri, DuPont; and Frederick Schoen, Harvard Medical School. The individual presenters are responsible for its substance.
Robert M. Nerem, Chair
Roundtable on Biomedical Engineering
Materials and Applications
Contents
Drug-Eluting Stents: Preclinical Testing Challenges, |
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TAXUS: A Polymer-Based Paclitaxel-Eluting Stent, |
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Cell-Matrix Cartilage Implants: A Clinician’s Perspective, |
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Cell Therapy for Cartilage Repair: Present and Future, |
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Cell-Matrix Cartilage Implants for Articular Repair and Replacement, |
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