Recombinant DNA Advisory Committee - 03/1-2/93 
assist the patient in understanding the sequence of events that they would undergo. A 
diagram has been submitted; however, the scale of the diagram is not proportional to 
time and should be revised. The investigators were commended for providing a 
comprehensive education program for health care workers that has been implemented 
for this study. 
Other Comments 
Dr. Parkman asked on what basis 56 days was chosen as the optimum time point for 
administration of the second dose of recombinant adenovirus. The reason that other 
investigators have proposed only a single administration is that the time frame for CFTR 
expression in humans is unknown. Although different adenovirus vectors will elicit 
varying degrees of immune response, Dr. Crystal has reported that the cotton rats have 
exhibited increased inflammatory responses for longer durations, in response to 
subsequent challenges of virus. What in vivo data exists with regard to the nature and 
duration of the inflammatory response with the proposed vector? Does the second 
challenge elicit a greater response than the first administration? Does the magnitude of 
the response increase with each consecutive administration? 
Ms. Meyers noted that the informed consent document should include statements about 
long term follow-up and a request for autopsy. Dr. Walters asked the investigators to 
explain the role of GTI in the proposed study. 
Presentation-Dr. Trapnell 
Dr. Trapnell described the progress that has been made in the sequencing of the 
adenovirus vector. Restriction mapping has been performed to evaluate the structure of 
the virus. Sequence analysis has been initiated for both the plasmid and the backbone of 
the parental virus. GTI will sequence the entire vector; however, there is uncertainty 
about the necessity of sequencing the entire vector. If the RAC requires the entire 
sequence, GTI will comply with the request. 
With regard to the fraction of the dose that will evaluated for sterility, Dr. Trapnell 
stated that the exact fraction has not yet been determined because GTI is still in the 
process of scaling up the production volume. GTI's goal is to test an entire patient 
dosage. Ms. Grossman asked about the size of a production lot. Dr. Trapnell responded 
that a production lot will be equal to several patient doses; however, the exact number of 
doses has not yet been determined. 
Dr. Miller asked if 1 helper virus particle can be detected in a 1 x 10 12 vector particles, 
which is the maximum proposed dosage. Dr. Trapnell said that he would first like to 
summarize the possible methods for detecting replication-competent particles. The first 
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