Recombinant DNA Adviaory Committee - 12/3-4/92 
In regard to this specific request, the RAC would lose any semblance of quality control 
in the field of gene therapy if it were to respond to compassionate use pleas that were 
not in conjunction with a protocol that had been reviewed by the committee in its final 
form. 
Presentation-Mr. Barton 
Mr. Barton stated that he reviewed the compassionate plea request from a legal 
perspective. Currently, the RAC cannot approve a request that has not been reviewed. 
Unless the RAC has reviewed a protocol that has received due public notice in the 
Federal Register , then the RAC should not approve the request. There is a possibility 
that the investigator would receive a court injunction if the public has not received due 
notice and been allowed to comment on the proposed action. 
The RAC ultimately considers the safety to the subject. Compassionate plea exemptions 
are an issue for the FDA to consider. In general, the FDA approval process does not 
apply to the Phase I testing; however, some investigators have applied prior to their 
investigational new drug (IND) submission. To date, the RAC has not considered any 
protocols that are beyond Phase I; therefore, adverse affects of the therapy must be 
considered. 
Unlike other biologic therapeutics, gene therapy presents additional concerns regarding 
third-party transmission. For example, the RAC has just approved several protocols for 
the treatment of CF using adenovirus vectors. Data suggests that these patients will 
continue to shed recombinant virus. What are the implications for the public? These 
safety concerns are reflective of the RACs role, namely, reassuring the public that this 
technology is going to be used in a way that will be safe. The RAC must consider to 
what extent future patients might be deprived of the benefits of a solid efficacy analysis 
based on the first generation of patients. 
Discussion 
Dr. Parkman said that he is basically in support of the relaxation of inclusion/exclusion 
criteria as outlined by Dr. Walters. A mechanism is already in place for the approval of 
minor modifications. The Points to Consider states that requests for minor modifications 
can be approved by the Chair of the RAC and that the Chair may consult with other 
committee members if necessary. This procedure is endorsed by IRBs. It is perfectly 
appropriate for an investigator to request a minor modification of an approved protocol. 
Ms. Meyers asked for clarification regarding the proposed request. Dr. Wivel stated that 
the request originated from a physician who wants to perform gene therapy on one 
patient. This request was submitted directly to the NIH Director. 
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Recombinant DNA Research, Volume 16 
