The NIH's recombinant DNA advisory committee (RAC) isconsidering methods to streamline its process for reviewinggene therapy and gene transfer protocols. One of the proposalsbrought up at last week's meeting -- but left hanging untilRAC's December gathering -- was to exempt certain types ofprotocols from review entirely. Another proposal -- even moreradical -- was to declare that RAC itself is obsolete.
"The RAC is struggling with how to draw the line between whatneeds to be reviewed and what doesn't," explained RACmember Leonard Post, vice president of experimental therapyat the Parke-Davis pharmaceutical division of Warner-LambertCo. (based in Morris Plains, N.J.) "There are various degrees ofcomfort and discomfort (among members of the RACsubcommittee on exemptions) with FDA as the sole regulatoryagency," Post told BioWorld.
The debate focuses on three categories of experiments forwhich the RAC has considerable experience and expertise: genemarking, experiments using irradiated cells and vaccines.
The only apparent agreement in the five-membersubcommittee was that repeat experiments and markingexperiments could be exempt from review. In the latter case,this would apply if "what is changing is not the marking butthe (medical) treatment of the (bone) marrow," RAC memberDoris Zallen, associate professor of science studies andhumanities at Virginia Polytechnic Institute and StateUniversity told BioWorld.
But exempt from what? Zallen, for example, prefers thatprotocols exempt from review by the full RAC should comebefore a subcommittee for expedited review, a new procedure,while Post would rather see them go straight to the FDA.
One problem with the latter, Zallen told BioWorld, is thatinvestigators have failed to report results of approvedexperiments to the RAC, although they are required to do soevery six months. If protocols go straight to FDA, theopportunity for learning through follow up on patients will belost.
Furthermore, RAC review would protect industry, Zallen said,since review "by the best experts in the country...would helpthem if there was legal liability."
Although only those investigators, companies or insitutionswho receive research dollars from government agencies arerequired to bring genetic therapy protocols before the RAC,companies almost always require assistance from academicinstitutions in order to conduct clinical trials.
Exemptions "would speed product development in a majorway," Gary McGarrity, vice president of Genetic Therapy, Inc. ofGaithersburg, Md., told BioWorld. McGarrity's company(NASDAQ:GTII) has developed a variety of vectors which havebeen used by "the majority of clinical trials approved by theNIH RAC," he said.
"My own opinion is that RAC ought to concentrate on novelaspects of gene therapy," Parke-Davis' Post told BioWorld.That's when RAC is at its best. For example, Post referred to theRAC meeting in early December at which it reviewed protocolsfor treating cystic fibrosis. "We spent a day on the issue ofusing adenovirus as a vector for gene therapy," he explained. Itwas the first gene therapy protocol to use an adenovirusvector, and new issues included safety of the vector, how totest the vector, and methods of delivery to the lung.
"I went to that meeting expecting none of those protocolswould be approved," Post told BioWorld. "But (they) werethoroughly discussed and debated, and I ended up voting forall three." All of the protocols were approved. Two of them --by principal investigators Ronald Crystal at the National Heart,Lung and Blood Institute and James Wilson at the University ofMichigan Medical Center -- called for the insertion of the cysticfibrosis transmembrane conductance regulator (CFTR) gene intothe lung using an adenovirus vector. A third -- sponsored byGenzyme Corp. (NASDAQ:GENZ) and the Howard Hughes MedicalInstitute at the University of Iowa Medical School and led byprincipal investigator Michael Welsh of Iowa -- involvedtargeting the CFTR gene to nasal epithelium rather than lungtissue.
Gene therapy pioneer and regular at RAC meetings W. FrenchAnderson of the University of Southern California also favorsextensive exeptions. "If there is any question (whether aprotocol is new) it should be reviewed, but the bulk ofprotocols aren't new," Anderson told BioWorld.
As for whether RAC might even be obsolete in its purpose andfunction, RAC member Nancy Buc, a partner in the Washington,D.C., law firm of Weil, Gotshal & Manges -- who made theprovocative suggestion in the first place -- told BioWorld that"it may be premature to answer that question, but it certainlyis time to start asking it."
Parker-Davis' Post expects the press of new research to forcethe issue. "That group meeting four times a year can't reviewall of gene therapy coming out of the U.S.," he said. He urgedinterested parties to make suggestions to RAC members or tothe Office of Recombinant DNA at NIH.
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.