Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Hirano inquired about the production and testing procedures for the VPC. Dr. 
McGarrity explained that there is a master cell bank of the VPC that contains several 
hundred cryopreserved ampules. Working cell banks are developed from the 
cryopreserved ampules. A working cell bank contains several hundred ampules. The 
final production lot of cells is taken from the working cell bank. Extensive quality 
control testing is performed at every step of this process. The VPC used in the proposed 
study will probably require two separate production runs. Since the cells are derived 
from the same working cell bank and the quality control standards are identical, there 
should be no differences between production runs. Dr. McGarrity explained that 
Genetic Therapy, Inc., is in the process of expanding the size of its production runs; 
therefore, alleviating any concerns associated with multiple processes. 
Dr. McGarrity addressed the issue of RCR testing. Depending on the production lot, 
between 2.5 and 5% of each lot is removed for testing purposes. Supernatants are 
assayed by S + L‘ and NIH3T3 amplification on Mus dunni cells. A portion of the VPC 
are cultured for 3 weeks to ensure that no breakout of RCR occurs. 
Committee Motion 
A motion was made by Dr. Hirano and seconded by Ms. Meyers to approve the protocol 
with the following stipulations: (1) Patient eligibility will be limited to those patients 
with measurable residual tumor on immediate post-operative imaging studies, i.e., CT or 
MRI scans. (2) Patient enrollment will be limited to 15 patients divided between the 
Iowa Methodist Medical Center and the University of Iowa. If a positive response is 
observed in any of the first 15 patients, the investigators may submit a request to treat an 
additional 15 patients. 
Dr. Geiduschek asked for clarification regarding the number of VPC that were removed 
for extended culture. With the recently approved compassionate use exemption for a 
human gene transfer protocol, the RAC will have to scrutinize the underlying safety 
issues more than they have in the past. Dr. McGarrity stated that approximately 2.5% of 
each production lot undergoes extended culture for 3 weeks in order to monitor potential 
RCR breakout. Dr. Post inquired as to how this percentage of the production lot 
compares to a patient dosage. Dr. McGarrity responded that 2.5% of a production lot 
represents approximately 4 to 5 patient doses. Each production lot contains between 1 x 
10 10 and 1 x 10 11 VPC. 
Dr. Miller asked why the RAC was including the stipulation about demonstration of 
residual tumor if this disease is uniformly fatal. Dr. Leventhal responded that the 
stipulation would probably not exclude very many patients because it is almost 
impossible to remove all of the patient's tumor by surgery. If the investigators proposes 
to establish efficacy based on stable disease for "X" period of time, then they must be 
Recombinant DNA Research, Volume 17 
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