Recombinant DNA Advisory Committee - 03/1-2/93 
However, one can approach the 0 particle limit by judicious sampling. 
Dr. Gunter stated that the dose of RCR which is disease-causing is still unknown and 
cited the RCR breakout which resulted in disease in the primate setting, i.e., lymphomas. 
Until the limits of RCR that cause disease are ascertained, the FDA does not feel that it 
can define absolute limits for sensitivity of RCR assays. Dr. Gunter said that he is 
personally uncomfortable with assessing the overall safety of RCR. 
Dr. Miller said that Dr. Gunter's statement is not fair to investigators, and that this issue 
is the basis for which the report was developed. The report provides useful significant 
detail about the RCR event which occurred in the monkeys and how the monkey 
situation translates to breakout levels of RCR. Dr. Gunter said that he differs with Dr. 
Anderson's interpretation because there have been only 5 monkeys that have been tested 
rigorously for RCR. The monkey database is too small at the current time to draw 
accurate conclusions. 
Dr. McGarrity described a reconstruction experiment designed to reproduce an RCR 
breakout. After 2 days in culture, the supernatant was removed from 10 RCR producing 
cells. The cells and the supernatant were then assayed separately for RCR breakout. 
Breakout was simulated in 2 to 3 days with this method. These studies are currently 
being refined to achieve a sensitivity level of detecting 1 RCR particle. When assays are 
perfected at this level, statistical analysis will probably translate into what actually 
happens when a breakout occurs, i.e., do the number of RCR particles increase 
tremendously or remain at low levels? These reconstruction experiments are the first 
attempt to develop a quantitative method for the detection of RCR. 
Dr. McGarrity described an RCR breakout that recently occurred in the laboratory 
setting. The breakout was detected when the RCR titer was approximately 200 particles 
per ml. This breakout was readily detected by the standard S + L‘ and NIH3T3 
amplification assays. 
Committee Motion 
A motion was made by Dr. Miller and seconded by Dr. Haselkorn to accept the report 
as a state-of-the-art guidance for investigators who are preparing retrovirus vectors for 
clinical use. The motion was approved by a vote of 17 in favor, 0 opposed, and no 
abstentions. 
XI. ADDITION TO THE POINTS TO CONSIDER OF THE NIH GUIDELINES 
REGARDING PROCEDURES FOR EXPEDITED REVIEW OF HUMAN GENE 
TRANSFER PROTOCOLS 
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Recombinant DNA Research, Volume 17 
