Recombinant DNA Advisory Committee - 09/14-15/92 
Ms. Buc commented that this is the first time that the RAC has been requested to 
reduce the physical containment level for a pathogenic expression vector system. Since 
RAC will likely receive more requests, the RAC should establish a Points to Consider 
document that outlines critical questions for investigators to respond to prior to seeking 
RAC approval for expression systems. A document of this nature would allow for a 
more disciplined and methodical review of these proposals. 
Dr. Parkman stated that this viral vector expression system should be reviewed based on 
whether the viral modification can be safely handled at BL2. However, there is the 
more general question of whether the parent virus, Semliki, is more suitably classified as 
a BL2 agent instead of BL3. Probably, it would have been more appropriate for the 
investigators to request a reclassification of the parent organism as opposed to the 
modified virus. 
Dr. Leventhal inquired about the data submitted from the laboratory that reported the 
one fatal case associated with SFV. The investigators state that antibodies to the virus 
were detected in four laboratory workers. How many were screened? What percentage 
does this represent? Dr. Temple responded that there is no extensive data regarding the 
incidence or frequency of symptomatic infections associated with the virus. 
Dr. Hirano asked if any of the laboratories that have already worked with this expression 
system have worked at BL3 containment. Dr. Temple explained that all of the 
laboratories, both in the U.S. and abroad, have used the system at BL2. Dr. Hirano 
noted that all of the data was generated using the baby hamster kidney system. Have 
experiments been performed on other cell lines to test if there is a higher probability of 
generating infectious particles? Dr. Liljestrom responded that the system has not been 
tested on any other cell lines. 
Committee Motion 
A motion was made by Dr. Schaechter and seconded by Dr. Hirano to defer approval of 
Dr. Temple's request to lower the physical containment level from BL3 to BL2 for the 
SFV vector expression system. Dr. Murray called for a vote. The motion to defer 
approval passed by a vote of 17 in favor, 1 opposed, and 2 abstentions. 
Dr. D. Miller suggested that the investigators should perform experiments to determine 
the frequency of infectious recombinants under the conditions of the expression system, 
i.e., 10 9 particles. Dr. Krogstad added that it would be useful to consult with 
investigators working with similar viruses at BL2 and establish the incidence of 
seropositivity among laboratory workers. 
V. PRESENTATION: FINANCIAL OBLIGATION OF RESEARCH INSTITUTIONS TO 
Recombinant DNA Research, Volume 16 
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