WASHINGTON _ The Recombinant DNA Advisory Committee(RAC) of the National Institutes of Health grudgingly agreed yesterdayto a shotgun marriage with the FDA _ but RAC members withheldfull approval until they see a detailed prenuptial agreement.The members voted 15-0, with one abstention, to approve therelationship in principle. But the lopsided outcome reflects pragmatismrather than enthusiasm."I agree with my colleagues that resistance to this change would befruitless," said Gary Chase, professor of Medicine at GeorgetownUniversity Medical Center here.The consolidation was ordered by NIH Director Harold Varmus andFDA Commissioner David Kessler in a bid to streamline review ofproposed gene therapies. Ironically, the merger comes as RACprepared to institute its own reforms, including accelerated review ofcertain clinical trial protocols.Although the proposal to consolidate the activities of the two bodiesarose at a July meeting of the National Task Force on AIDS DrugDevelopment, it reflects overall dissatisfaction with federal drugapproval procedures both within and outside government.On Monday, Varmus told RAC members that he personally was sotroubled by complaints of delays and unclear RAC criteria raised at theAIDS meeting that he would establish an ad hoc external commissionto review RAC's mission."We need to consider what the domain of [RAC's] activity should be inthe future," Varmus told the committee members. "This issue becomesparticularly important as we move to an expedited review protocol."Robertson Parkman, head of research immunology and bone marrowtransplantation at Childrens Hospital of Los Angeles, fretted that theproposed changes would, paradoxically, make life tougher forinvestigators, not easier."Consistency within the RAC is crucial," Parkman said. "It's importantthat whatever criteria we use to evaluate protocols are clearlyannunciated, so that investigators know what information is required.And, conversely, so that the results of not having required informationis also quite clear."Changing the rules in the middle of the road does not necessarilybenefit anyone," he said.Abbey Meyers, director of the National Organization for RareDisorders, ventured her concern that "if these protocols are notreviewed in public," ill-conceived studies could ultimately put researchsubjects at risk."The investigator has to protect his career and university," she said,"the FDA has to protect its regulatory authority, the company has avested interest in the research succeeding, and there's nobody there tospeak for the patient."Varmus assured the members that he would not abolish the two-decadeold institution, which was established in the mid-1970's by then-NIHdirector Donald Fredrickson to allay mounting public concern thatscientists using new genetic techniques would unleash mutant genesinto the human population."Despite suggestions that this arrangement heralds the end of RAC," hesaid, "I assure you, that's not the case." Instead, Varmus said, he hopedthe reforms would free RAC to focus on more universal matters, suchas establishing criteria for prenatal gene therapy and the ramificationsof genetic techniques to promote individual enhancement.Under the latest version of the consolidation proposal _ which wasrevised even between sessions of the two-day RAC meeting _investigators would be required to submit all of their documentation tothe FDA.The documentation would include an investigational new drug (IND)application, research protocol, informed consent form and the requiredresponses to RAC's standard list of questions about the proposedresearch.The FDA would log in the material, and then send copies of everythingbut the proprietary IND to the NIH's Office of Recombinant DNAActivities, which is RAC's administrative headquarters.Phillip Noguchi, of the FDA's division of Cellular and Gene Therapies,in Rockville, Md., assured RAC members yesterday that the agencywould like to act in concert with RAC, although the details must still beworked out. "We are proposing something quite radical," Noguchi said."Cooperation between two agencies of government."Ideally, he said, the FDA could relieve the committee of the burden ofreviewing every gene therapy protocol, without usurping RAC'sprerogative to review those that pose scientific, ethical or moralconundrums that the committee deems would benefit from publicdiscussion.Noguchi also said the FDA seeks to preserve the full public disclosurethat has been central to RAC's activities. He assured RAC membersthat disclosure also benefits the FDA, by enabling agency bureaucratsto seek guidance on and publicly discuss material that would be strictlyconfidential if submitted to the agency in an IND.Noguchi, however, told BioWorld Today that he could not guaranteethat RAC-required material submitted through the FDA would remainpublicly available because he was not familiar enough with the letter ofFDA law."If this proposal runs into snags," he said, "we would propose that thecurrent process be sustained with changes to streamline it as much aspossible." n

-- Steve Sternberg Special To BioWorld Today

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