Recombinant DNA Advisory Committee- 9/12-13/94 
review process in response to the National AIDS Task Force is a continuation of the 
RAC’s own Accelerated, Review reform. Mr. Capron was comfortable with the 
arrangement that all submissions would be routed through FDA. But he still expressed 
concern about the current state of the art regarding patient outcome in the gene therapy 
trials, e.g, safety and other patient follow-up data. Given the relative paucity of data, 
lesser scrutiny by RAC may not be justified. Ms. Meyers asked if efficacy criteria should 
be required for so many cytokine studies. Dr. Parkman said no efficacy has to be 
demonstrated in these Phase I studies since the patient’s cancer is very often too advanced 
to respond to gene therapy; efficacy is not the primary endpoint of these trials. 
Committee Motion 
Dr. Walters asked if there was a motion for approving the concept of consolidated review. 
Dr. Miller said he would be ready to propose such a motion. He said that the revised 
FDA proposal has addressed his main concern that the RAC will maintain control over its 
Points to Consider , and it is not important which agency receives submissions. At present, 
the RAC-approved categories of Accelerated Review protocols can be adopted as a 
guideline for proposals that will not require RAC review. Dr. Parkman reminded that the 
categories served only as guidelines. For unusual experiments, even those falling within 
categories such as the administration of retinoblastoma cells secreting interleukin-2 into a 
child’s eye, would not be exempted from RAC review. Dr. Miller said that he would vote 
for the proposed guideline changes within the general concept of NIH/FDA consolidated 
review. Specifically, he would sanction the revised FDA proposal submitted by Dr. 
Noguchi. Dr. Zallen seconded the motion. 
Discussion 
Dr. Walters considered that it was important to keep the Points to Consider within the 
NIH Guidelines. The document has evolved in the last 10 years under the purview of the 
RAC. Ms. Meyers expressed her remaining concern about lack of ethicists in FDA staff 
in dealing with ethic issues even for those "me too" experiments in regard to the Informed 
Consent documents. Dr. Noguchi assured Ms. Meyers if there is any question concerning 
safety and subjects’ rights, the RAC will be consulted. These issues are of paramount 
importance to FDA’s review. Dr. Noguchi mentioned as an example, the ethical dilemma 
in their approval of gene therapy for newborn infants in the adenosine deaminase (ADA) 
deficiency protocol. The RAC provided guidelines for the FDA process. 
Dr. Zallen asked Dr. Noguchi two questions: (1) The investigators presumably are still 
required to produce as many documents as in the old review system. Will the new system 
be more efficient? (2) The RAC will continue to evolve its Points to Consider. Will FDA 
amend its document? Dr. Noguchi said that FDA’s intent is to abide with the Points of 
Consider as much as possible and has no intention of unilaterally revising this document 
since it is a part of the NIH Guidelines. Responding to a question by Dr. Miller, Dr. 
Noguchi said that FDA will keep its own Points to Consider dealing with the vector 
manufacturing process. The joint review process will be developed with public, academic, 
and corporate inputs to make it as efficient as possible. Dr. Ross suggested re-evaluation 
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Recombinant DNA Research, Volume 20 
