Recombinant DMA Advisory Committee - 03/1-2/93 
backbone. They should describe the exact portions of the vector that will be sequenced. 
Also, the investigators need to present their quantitative PCR data demonstrating that 
they are able to detect 1 wild-type virus particle per 1 x 10 8 recombinant adenovirus 
particles. 
Ms. Grossman said that there are several questions that the investigators should address 
during their oral presentation. What fraction of each dose will be evaluated for sterility, 
mycoplasma and replication-competent adenovirus? How will in vivo toxicity be 
determined? Toxicity studies have been performed in cotton rats; however, it would be 
preferable if these studies would be performed in a larger animal model. She stated a 
concern that the investigators are attempting to assess biological efficacy and safety of a 
single administration of recombinant adenovirus, and then they propose to rechallenge 
the patient with a second dose of virus 2 months later. The second administration of 
recombinant adenovirus may not be feasible and/or necessary. This second dosage may 
be putting patients at an additional risk since the effects of a single administration are 
unknown. She inquired whether recombinant adenovirus has ever been administered to 
a large animal model and an attempt made to obtain CFTR-expressing cells? Is there 
data demonstrating the investigator's ability to administer the recombinant adenovirus 
and recover gene-transduced cells from brushings? 
Ms. Grossman noted that the inclusion/exclusion criteria limits eligibility for this 
protocol to patients greater than 18 years of age; however, the experiments will be 
performed at the Cincinnati Children's Hospital. Are there any necessary measures that 
must be taken to treat adults at a pediatric hospital? Who will be the primary 
physician? 
Review--Dr. Haselkorn 
Dr. Haselkorn stated that he was originally concerned about the necessity for frequent 
biopsies and the degree of discomfort associated with these procedures. The 
investigators did satisfactorily respond to these concerns by reducing the frequency of the 
bronchoscopies and biopsies. 
Review-Dr. Zallen 
Dr. Zallen said that she had the same initial concerns as Dr. Haselkorn regarding the 
frequency of biopsies, and that she was satisfied with the revised schedule. For 
clarification purposes, the investigators need to explain the necessity for the large 
number of x-rays and to explain their ability to reliably detect improvement in a lung 
that is already severely damaged. 
Dr. Zallen stated that her written comments requested that a diagram be included to 
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