Recombinant DNA Advisory Committee - 09/14-15/92 
Dr. Parkman seconded the motion only to speak against the safety testing requirements 
proposed by Dr. Geiduschek. Dr. Parkman said that the RAC cannot change the 
standards by which they review protocols at the same meeting. Although it is likely that 
the FDA may change their vector testing requirements for the presence of replication 
competent virus, the RAC should remain consistent in its requirements for testing at this 
time. 
Dr. Doi asked the time-frame that would be required to perform the additional 
experiments suggested by Dr. Geiduschek. Dr. D. Miller said that they do not have the 
option of returning to the stocks and reassaying for helper virus. Those cells no longer 
exist, the vector supernatant stocks are already in storage. In the future when more 
supernatants are produced, there will be the option to perform the suggested assays. 
Dr. Post asked if the NIH 3T3 amplification assay would increase the level of sensitivity 
to detect one particle per 300 milliliters. Dr. D. Miller stated that the NIH 3T3 assay 
would not provide this information; however, one culture flask which makes 
approximately 300 milliliters of supernatant was passaged, cultured long-term, and 
assayed for replication competent helper virus. Dr. Krogstad asked about the degree of 
certainty that one infectious particle will be detected by this method. Dr. D. Miller 
explained that at the time of supernatant harvest, the producer cells are confluent. If 
one viral particle is present at this stage, that particle should replicate to detectable 
levels within several weeks following trypsinization and reculture of these cells. Dr. D. 
Miller described experiments performed with PA317 cells in which a confluent culture 
was spiked with helper virus. Within two weeks, the number of helper virus particles 
increased to 10 7 particles. This level of virus is readily detectable by PCR. 
Dr. D. Miller said that investigators will have to provide data according to the standards 
established by FDA. The RAC should discuss the issue of helper virus. Although FDA 
will ultimately develop the required testing standards, this issue should be conducted in 
public. The RAC provides such an open forum to discuss this issue unlike the FDA. 
Dr. Aebersold added that the FDA's Points to Consider in Somatic Cell Gene Therapy 
document was established based on public review and comments. FDA reviews gene 
therapy confidentially; however, the document which provides the basis for this review 
was established publicly. Dr. Post asked Dr. Aebersold how long these public meetings 
would continue. Dr. Aebersold responded there is no expectation that FDA's public 
meetings will be abandoned. 
Amendment-Mr. Barton 
Mr. Barton moved that the motion made by Dr. Geiduschek should be amended to 
delete the requirement for the special review of the safety of the vector. The amended 
motion would merely approve the protocols with the expectation that the FDA will set 
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Recombinant DNA Research, Volume 16 
