Recombinant DNA Advisory Committee - 01/14/93 
could be assured that Dr. Royston submitted significant documentation, other than the 
information sent to the NIH. Dr. Woodcock said that she could define the FDA's 
criteria for approving a gene therapy biologic for a Phase I trial. Dr. Post asked Dr. 
Woodcock to be as specific as possible about this particular approval. Dr. Woodcock 
said that she could not provide that information. Dr. Post asked Dr. Royston to respond 
to this question during his statement. 
Dr. Woodcock stated that the vector proposed by Dr. Royston was already approved by 
the NIH and the FDA. Dr. Post said that the vector had been approved for use in Dr. 
Gansbacher's protocol. However, the cells have not been approved, which is an 
important distinction. Dr. Woodcock stated that any concerns the RAC would have 
about the cells probably focus on the activity and effectiveness of the cells rather than 
biosafety considerations. Dr. Post said that the safety of these cells is a primary 
consideration. 
Dr. Woodcock stated that it is plausible that the RAC and the FDA would come to 
different conclusions. In fact, on every single gene therapy protocol the FDA has 
reviewed, there has been internal scientific disagreement. Dr. Royston's request is a sort 
of hybrid request because of the element of the cells. The investigational vector has 
been approved for a Phase I trial. However, the use of this vector was not simply an 
extension at a different geographic site. Obviously, Dr. Royston proposed to use the 
vector in a different manner than Dr. Gansbacher. 
Dr. Geiduschek asked Dr. Woodcock if the FDA's approval of drugs that have never 
been approved for investigational use refers to the U.S. or anywhere in the world. Dr. 
Woodcock responded that these rare exemptions have been granted for drugs that have 
never been used in any Phase I trial in the world. However, the FDA is very 
discouraging about such uses, because there is no evidence of efficacy and no toxicity 
data is available on these agents. 
Dr. Geiduschek asked for clarification regarding the criteria that the FDA uses to grant 
such approvals. Does the FDA grant compassionate plea exemptions for materials 
whose properties in humans are unknown? Dr. Woodcock responded that the FDA 
requires the same safety information whether the protocol is directed toward a specific 
patient or a total Phase I trial. 
Dr. Haselkorn asked Dr. Woodcock if the FDA was provided any information on the 
safety of the transduced cells to be used in Dr. Royston's protocol. Dr. Woodcock said 
that the FDA outlined their requirements for safety testing previously, both for 
adventitious agent testing and for expression of the desired gene. Every lot of 
investigational biological agents administered to humans must meet a set of lot release 
criteria. These criteria are primarily safety and potency testing. Dr. Woodcock said that 
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Recombinant DNA Research, Volume 17 
