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RECOMBINANT DNA ADVISORY COMMITTEE Minutes of Meeting December 15-16, 1997

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RECOMBINANT DNA ADVISORY COMMITTEE Minutes of Meeting December 15-16, 1997 RECOMBINANT DNA ADVISORY COMMITTEE Minutes of Meeting December 15-16, 1997 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health TABLE OF CONTENTS I. Call to Order and Opening Remarks/Mickelson II. RAC Forum on New Technologies III. Food and Drug Administration (FDA) Presentation: Discussion of the Risks of Gonadal Distribution and Inadvertent Germ Line Integration in Patients Receiving Direct Administration of Gene Therapy Vectors IV. Call to Order/Mickelson V. Minutes of the September 12, 1997, Meeting/Ando, Greenblatt VI. Update on Data Management/Greenblatt VII. Amendment to Institutional Biosafety Committee Approvals of Experiments Involving Transgenic Rodents Under Section III of the NIH Guidelines/Aguilar-Cordova VIII. Amendment to Appendix K, Physical Containment for Large Scale Uses of Organisms Containing Recombinant DNA Molecules/McGarrity IX. Amendment to Section III-D-6, Experiments Involving More than 10 Liters of Culture/Knazek X. Human Gene Transfer Protocol #9708-209 entitled: Systemic and Respiratory Immune Response to Administration of an Adenovirus Type 5 Gene Transfer Vector (AdGVCD.10)/Harvey, Crystal XI. Human Gene Transfer Protocol #9711-221 entitled: Phase I Study of Direct Administration of a Replication-Deficient Adenovirus Vector (AdGVVEGF121.10) Containing the VEGF121 cDNA to the Ischemic Myocardium of Individuals with Life Threatening Diffuse Coronary Artery Disease/Crystal XII. Amendment to Appendix M-I, Submission Requirements--Human Gene Transfer Experiments Regarding the Timing of Institutional Biosafety Committee and Institutional Review Board Page 1 Approvals/Markert XIII. Human Gene Transfer Protocol #9708-211 entitled: Gene Therapy for Canavan Disease/Seashore XIV. Amendment to Appendix M-I, Submission Requirements--Human Gene Transfer Experiments Regarding Deadline Submission for RAC Review/McIvor XV. Chair’s Closing Remarks/Mickelson XVI. Future Meeting Dates/Mickelson XVII. Adjournment/Mickelson The Recombinant DNA Advisory Committee (RAC) was convened for its sixty-ninth meeting at 9:00 a.m. on December 15, 1997, at the National Institutes of Health NIH),( Building 31, Conference Room 10, 9000 Rockville Pike, Bethesda, Maryland 20892. Dr. Claudia Mickelson (Chair) presided. In accordance with Public Law 92-463, the meeting was open to the public on December 15 from 9:00 a.m. until 7:00 p.m and December 16 from 8:30 a.m. to 6:00 p.m. The following were present for all or part of the meeting: Committee Members: C. Estuardo Aguilar-Cordova, Texas Childrens Hospital Dale G. Ando, Cell Genesys, Inc. Jon W. Gordon, Mt. Sinai School of Medicine Jay J. Greenblatt, National Institutes of Health Michael M.C. Lai, University of Southern California Leslie A. Leinwand, University of Colorado M. Therese Lysaught, University of Dayton Ruth Macklin, Albert Einstein College of Medicine M. Louise Markert, Duke University Medical Center R. Scott McIvor, University of Minnesota Claudia A. Mickelson, Massachusetts Institute of Technology Karen Rothenberg, University of Maryland School of Law Inder M. Verma, The Salk Institute Jon A. Wolff, University of Wisconsin Medical School Executive Secretary: Debra W. Knorr, National Institutes of Health A committee roster is attached (Attachment I). Non-Voting Representatives: F. William Dommel, Jr., Office of Protection from Research Risks Daniel D. Jones, U.S. Department of Agriculture Page 2 Philip Noguchi, Food and Drug Administration National Institutes of Health staff: Melissa Ashlock, NHGRI Bobbi Bennett, OD Kristina Borror, OD Diane Bronzert, NCI Jeffrey Cohen, NIAID Cheryl Corsaro, NHGRI Greg Downing, OD Joseph Gallelli, CC Harold Ginsberg, NIAID Roberta Haber, NIDDK Christine Ireland, OD Julie Kaneshiro, OD Robin Kawazoe, OD Richard Knazek, NCRR Becky Lawson, OD Carol Manning, NCI Catherine McKeon, NIDDK Mikel Miller, OD Monique Mansoura, NHGRI Pearl O’Rourke, OD Gene Rosenthal, OD Aiman Shalabi, NCI Thomas Shih, OD Sonia Skarlatos, NHLBI Lana Skirboll, OD Stephen Straus, NIAID Harold Varmus, OD Others: Victoria Allgood, GeneMedicine, Inc. Robert Anderson, Food and Drug Administration W. French Anderson, University of Southern California Kameron Balzer, Genentech, Inc. Steven Bauer, Food and Drug Administration Bridget Binko, Cell Genesys, Inc. Flavia Borellini , MA BioServices Xandra Breakefield, Massachusetts General Hospital Judi Buckalew, Senator Kay Bailey Hutchinson’s Office (Texas) Jeff Carey, Genetic Therapy, Inc. Ira Carmen, University of Illinois Joy Cavagnaro, Human Genome Sciences Yung-Mien Chang, Genetic Therapy, Inc. Yara Cheikh, Cheikh Daniela Cirillo, Stanford University Hillel Cohen, Merck Research Laboratories Page 3 Ronald Crystal, Cornell University Kenneth Culver, Codon Pharmaceuticals, Inc. John Cutt, Novartis Pharmaceuticals Corporation Barbara Davies, Pro-Neuron, Inc. Laura Dely, FDA Week Ronald Dorazio, Genetix Pharmaceuticals, Inc. Anne Dunne, Strategic Results, LLC Matthew During, University of Auckland, New Zealand Ross Durland, GeneMedicine, Inc. Suzanne Epstein, Food and Drug Administration Mitchell Finer, Cell Genesys, Inc. Gary Gamerman, Fenwick and West Joseph Glorioso, University of Pittsburgh Elissa Grabowski, Dewe Rogerson, Inc. Tina Grasso, GenVec Stephen Hoffman, Naval Medical Research Russell Howard, Maxygen Lee Huang, Rhone-Poulenc Rorer Jeffrey Isner, Tufts University John Jafari, Genetic Therapy, Inc. Joan Keiser, Parke-Davis Pharmaceutical Research Imre Kovesdi, GenVec Larry Kowal, Genetic Therapy, Inc. Steven Kradjian, Vical, Inc. Mike Kulkarx, Aurx, Inc. LaVonne Lang, Parke-Davis Pharmaceutical Research Michael Langan, National Organization for Rare Disorders Fred Ledley, Variagenics, Inc. Brian Ledwith, Merck Research Laboratories Russette Lyons, Genetic Therapy, Inc. Carol Marcus-Sekura, Biotechnology Assessment Services, Inc. Reuben Matalon, University of Texas Medical Branch Gerard McGarrity, Genetic Therapy, Inc. Andra Miller, Food and Drug Administration Margaret Moore, NeuroVir, Inc., Canada Carolyn Nagler, PSI International Luigi Naldini, Cell Genesys, Inc. John Norman, Vical, Inc. Marina O’Reilly, Genetic Therapy, Inc. Sheryl Osborne, NeuroVir, Inc., Canada Jeffrey Ostrove, NeuroVir, Inc., Canada Amy Patterson, Food and Drug Administration Nick Pelliccione , Schering-Plough Corporation Janet Peterson, University of Maryland Anne Pilaro, Food and Drug Administration Leonard Post, Parke-Davis Pharmaceutical Research Toni Putnam, Public Andrew Quon, American Association of Medical Colleges Rafel Rieves, Food and Drug Administration Bernard Roizman, University of Chicago Page 4 Joseph Rokovich, Pangaea Pharmaceuticals, Inc. Todd Rosengart, Cornell University Dean Rupp, Yale University Margaret Samyn, Parke-Davis Pharmaceutical Research Victor Santamarina, Genetic Therapy, Inc. Jack Schaumberg, GeneMedicine, Inc. Mercedes Serabian, Food and Drug Administration Tomiko Shimada, Ambience Awareness International, Inc. Stephanie Simek, Food and Drug Administration Thomas Smart, GenVec Frank Tufaro, NeuroVir, Inc., Canada Andrew Uprichard, Parke-Davis Pharmaceutical Research Dominick Vacante, Magenta Corporation Edward Wagner, University of California at Irvine Lisa White, The Blue Sheet Carolyn Wilson, Food and Drug Administration Chris Wysocki, Genetic Therapy, Inc. Grant Yonehiro, GenVec I. CALL TO ORDER AND OPENING REMARKS/DR. MICKELSON Dr. Claudia A. Mickelson, Chair of the Recombinant DNA Advisory Committee (RAC), called the meeting to order. She stated that due notice of the meeting, and the proposed actions under theNIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines), were both published in the Federal Register on October 16, 1997 (62 FR 53908) and on November 19, 1997 (62 FR 61862). Dr. Mickelson welcomed Mr. F. William Dommel, J.D., Director of Education, Office of Protection from Research Risks (OPRR), as a non-voting agency representative; and Inder M. Verma, Ph.D., Professor, Laboratory of Genetics, The Salk Institute, La Jolla, California, as a new RAC member. Dr. Mickelson stated that the Environmental Assessment and Finding of No Significant Impact was completed, and that a notice of the availability of this document was published in the Federal Register on November 4, 1997 (62 FR 59720). She noted that the final action to promulgate the amendments to the NIH Guidelines regarding NIH oversight of human gene transfer research was published in the Federal Register on October 31, 1997 (62 FR 59032). Under the new NIH Guidelines the RAC no longer has approval authority for human gene transfer protocols. The RAC can review novel protocols and it can make recommendation(s). Any RAC recommendations may be forwarded to the NIH Director, the principal investigator, the sponsoring institution, and other Department of Health and Human Services components, as appropriate. Dr. Mickelson stated that the proposed actions to be considered by the RAC are amendments to theNIH Guidelines regarding: (1) Institutional Biosafety Committee (IBC) approval of experiments involving transgenic rodents, (2) Appendix K regarding large scale production of human gene transfer vectors, (3) Section III-D-6 regarding experiments of more than 10 liters of culture, (4) Appendix M-I regarding the timing issue of IBC and Institutional Review Board (IRB) approvals, and (5) Appendix M-I regarding submission deadline of human gene transfer protocol submission to the NIH Office of Recombinant DNA Activities (ORDA). Dr. Mickelson noted that two additional actions
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