Recombinant DNA Advisory Committee - 09/14-15/92 
potential benefit of the patient would be improved treatment of HIV infection using a 
new therapeutic approach. This statement is overly optimistic since it is not known if the 
procedure will provide any potential benefit to the patient. Dr. Walker disagreed with 
this conclusion noting that the ADA data suggests that lymphocyte transfer offers a 
potential benefit to patients. Potential is the key word. Dr. D. Miller suggested that the 
therapeutic benefit comments should focus on the gene transfer aspects of the protocol. 
With regard to the vector safety testing requirements, Dr. D. Miller suggested that the 
RAC should focus on the issue of long-term cultivation of packaging cell lines. Is long- 
term cultivation for two to three weeks following harvest of vector supernatant the most 
sensitive test that can be performed to detect the presence of helper virus? This post- 
harvest culture criteria would be an acceptable standard for the RAC to adopt. 
Although the RAC could require investigators to co-cultivate supernatants with a cell 
line that would rescue helper virus, Dr. D. Miller suggested that such a requirement is 
probably not necessary for the RAC to request. Dr. Blaese noted that the FDA had a 
meeting today regarding revised standards for helper virus testing and suggested that Dr. 
Tolstoshev of GTI could comment on the current standards that are being employed by 
their company. Dr. Blaese stated that there is no indication from any experiments that 
have been performed to date that the current techniques or technologies for detecting 
helper virus contamination are not sufficient. 
Dr. Tolstoshev commented on the issue of helper virus testing. GTI, which supplies 
many investigators with retroviral vector supernatants, has adopted the standard of 
culturing all packaging cell lines for three weeks following harvest of the vector 
supernatant and to monitor for helper virus during this period. If the RAC and FDA 
agree that these assay standards are adequate, then GTI has an abundance of vector 
material to provide for current trials. GTI has incorporated additional safety 
modifications to increase the specificity of helper virus assays. Regarding co-cultivation 
assays, these assays have not yet been validated. Dr. Parkman asked if aliquots were 
frozen from past production runs? Dr. Tolstoshev responded that cells were not 
generally frozen from past runs. Dr. Post asked if the FDA has an official position on 
standards for helper virus testing? Dr. Henry Miller of the FDA stated that the Center 
for Biologies is discussing the relevant issues today, and that he would rather not 
comment on the issue at this point in time. Dr. Post asked Dr. H. Miller if he could 
present an update of the FDA meeting during the afternoon RAC session. Dr. H. Miller 
answered that he would try to obtain the relevant information and report back to the 
RAC. 
Dr. Chase said that the investigators have stated that there are 24 discordant identical 
twin pairs and that they represent a relatively complete catchment of the U.S. 
population. Is this assertion supported by formal computations? Dr. Lane explained 
that registry may not be the most appropriate term to use. Actually, there are probably 
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