Recombinant DNA Advisory Committee - 09/14-15/92 
with this virus. This virus is endemic to Central Africa and some areas of Switzerland. 
Generally, the symptoms are mild and nondifferentiable from the acute phase of other 
febrile illnesses such as acute influenza and early stage malaria. Although SFV is 
thought to be relatively safe, BL3 containment was designated because there could be 
some low incidence of fatal infection. 
Dr. Post said that it is unclear as to why there is a different containment classification for 
SFV than Sindbis virus. There are a number of investigators who are currently using 
Sindbis vector systems as BL2 containment levels. Why have the investigators chosen to 
develop an SFV expression system instead of the Sindbis vector system? Dr. Liljestrom 
explained that his laboratory has extensive experience with SFV, and that in his opinion, 
Sindbis vectors do not function properly. Sindbis titers can not be obtained as high as 
those with SFV, probably because Sindbis does not replicate as efficiently. Dr. Temple 
noted that both of these are pathogens, but the only difference is that Sindbis has never 
had any fatalities associated with it. 
Dr. Post added that pathogenicity is an important issue and reminded the RAC that 
there are a number of organisms classified for use at the BL2 level of containment that 
have proven to be fatal, e.g., Vaccinia. Dr. Post said it is unclear how the classification 
of pathogenic organisms in Appendix B of the NIH Guidelines was assigned. Apparently, 
the difference between a BL2 and BL3 classification is subjective. Dr. Wivel noted that 
Appendix B is largely based on Centers for Disease Control (CDC) data which considers 
a number of factors. The basis for most of the pathogenic classifications is based on 
data published in. Biosafety in Microbiological & Biomedical Laboratories published by the 
NIH and CDC. This document categorizes microorganisms based on the severity of 
illness, risk of infection, and lability of the infectious agent and focuses on human and 
animal pathogens. Dr. Temple noted that the NIH/CDC manual states that SFV can be 
safely handled for most laboratory uses as BL2; however, this classification was made 
prior to the fatality associated with its use. The latest edition of this manual was 
published in 1988. Mr. Barton inquired as to whether a distinction could be made 
regarding BL2 and BL3 classification if an organism is indigenous to the U.S. or not. 
Dr. Wivel answered that while this may be a consideration, classification is based in part 
on the availability of a vaccine against a particular microorganism. 
Dr. Haselkorn asked the investigators to review the practical differences between BL2 
and BL3 physical containment. Dr. Wivel explained that for BL3 containment, there is a 
requirement for negative air flow and that an autoclave be in the laboratory, not down 
the hall. Dr. Murray directed the members of the RAC that the definitions could be 
found on page 16974 of the (57 FR 19512). Dr. Geiduschek asked the investigators if 
the issue of commercialization is linked to a BL2 classification versus BL3. Dr. Temple 
said that Life Technologies, Inc., has no intention of distributing the kit unless it has a 
BL2 designation. 
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