Recombinant DNA Advisory Committee - 12/1-2/94 
accepted the RAC’s recommendation, FDA legal counsel has not yet agreed to the language of these proposed 
actions based on concern regarding the release of proprietary information. The NIH and FDA are continuing 
discussion on these actions to resolve these issues. 
Dr. Noguchi stated that the FDA endorses the RAC’s Data Management activities and discussion of pertinent 
global issues, e.g., in utero gene therapy. The NIH/FDA consolidated review process will not preclude public 
disclosure of information that is currently submitted to the RAC. He stressed the importance of the RAC 
semiannual data reporting process since the FDA does not have an equivalent process for regular reporting. 
On October 27, 1994, the FDA published proposed amendments to 21 CFR Part 312, Investigational New 
Drug (IND) regulations, in the Federal Register (59 FR 54046). These proposed amendments would require 
semiannual data reporting (currently annual) to the FDA and would emphasize adverse event reporting. 
There is an absolute necessity for "real-time" reporting of adverse events. The FDA will continue to propose 
amendments to the IND regulations in order to accommodate public disclosure of adverse event reporting. 
Other Comments 
Dr. Motulsky noted the following statement in Dr. Goldhammer’s letter, "Since all gene therapy protocols will 
now be submitted initially to FDA, the provision should exist for sponsors not receiving NIH funding to elect 
for or against NIH-RAC review." Dr. Motulsky inquired whether the NIH/FDA consolidated review process 
would change the current status of RAC review. Dr. Wivel responded that any industry sponsor that 
collaborates with an investigator whose institution receives any funding from the NIH for recombinant DNA 
research is required to comply with the NIH Guidelines. Therefore, any such collaborative efforts will still 
require NIH oversight. Under the consolidated review, however, there will be protocols that will require 
submission to NIH Office of Recombinant DNA Activities (ORDA) but will be exempt from full RAC review. 
Such protocols will be reviewed by the FDA while the documentation is maintained by both the NIH and 
FDA. 
Dr. Straus noted that any company that voluntarily submits a protocol for RAC review should accept 
responsibility for data management and other follow-up activities. 
Dr. Miller inquired about the human studies involving vaccinia virus vectors that were not reviewed by the 
RAC. Dr. Wivel explained that these vaccinia studies were initiated prior to the revision of the footnote in 
Section V-U of the NIH Guidelines. The recently revised definition restricts exempt vaccines to vector- 
encoded "microbial" immunogens. This revised definition does not exempt the "cancer vaccine" protocols. 
Ms. Meyers asked if a company could conduct human "enhancement" gene transfer experiments and not be 
required to comply with the NIH Guidelines , e.g., experiments that introduce a "fat" gene for the treatment of 
obese people or introduce a growth hormone gene to "treat" short stature. Dr. Wivel responded that NIH 
would not require review of such studies; however, FDA review is mandatory. Ms. Meyers remarked that the 
FDA does not review ethical issues. Dr. Noguchi responded that the FDA requires Institutional Review Board 
(IRB) review of such protocols. The FDA reviews Informed Consent documents on an ad hoc basis. The 
FDA retains the option to bring any protocol for public discussion by an FDA advisory committee. The FDA 
can require RAC review for such proposals under the NIH/FDA consolidated review process. 
Ms. Meyers inquired whether the FDA could bring such an enhancement gene therapy protocol to the RAC 
without explicit permission from the sponsoring company. Dr. Noguchi answered that the FDA can obtain 
advice from any review body that is deemed to be appropriate. Ms. Meyers asked if such a review would 
require a closed RAC session. Dr. Noguchi responded that the FDA’s intention would be to have open 
discussion within current FDA regulations. There is no ready mechanism to demand that a company commit 
to an open meeting. Ms. Meyers expressed concern about the likelihood that investigators who are not 
collaborating with an NIH-funded institution could conduct germ line gene therapy or enhancement gene 
therapy without public awareness or discussion. Dr. Noguchi remarked that there is the legal possibility that 
such experiments could be conducted without public disclosure. 
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Recombinant DNA Research, Volume 20 
