Recombinant DNA Advisory Committee - 12/3-4/92 
In no way is the FDA stating that they will require that all of these assays should be 
performed for the detection of retrovirus. In addition, the TEM assay is only offered as 
a suggestion. TEM offers the additional measure that unknown retrovirus particles can 
be detected. 
Dr. Kahn responded to Dr. Anderson's question regarding the need for more sensitive 
assays. Gene therapy products are unique because of the fact that there are no 
inactivation procedures as with other biological products, e.g., monoclonal antibodies. 
The FDA's safety concerns are greatly heightened due to the recent results regarding the 
generation of RCR. Therefore, there is a need for the development of new, more 
sensitive assays. If more sensitive assays are established, there will be an obligation to 
use these testing methods as they become available. 
Dr. D. Miller said that the distinctions drawn between monoclonal antibody production 
and vector production are not as clear as Dr. Kahn suggests. The FDA limits the 
amount of contaminating DNA that can be present in monoclonal antibody producer 
cells. DNA could be transferred for Chinese hamster ovary (CHO) cells during the 
production of recombinant products that could in turn be taken up by other cells. Dr. D. 
Miller stated that retroviruses are not any more unique than monoclonal antibodies. 
Viruses can be inactivated from these biological products, but the DNA remains; and the 
FDA is concerned about this level of contamination. 
Dr. D. Miller said that the experiment proposed by Dr. Parkman is ideal and should be 
performed to determine how rapidly the virus spreads through a culture and the 
feasibility of performing this assay on the entire production lot. If the additional 
procedure costs less than $5,000, than it is probably reasonable to perform. However, if 
the proposed testing were to cost $100,000, this cost would be prohibitive. The RAC is 
charged with developing testing procedures within reason that will provide the greatest 
safety possible. Dr. D. Miller stated that it is unreasonable for the FDA to pursue more 
sensitive assays in the absence of any observable risk. 
Dr. Geiduschek said that he is satisfied to know that this issue will be pursued vigorously 
in the near future. He asked about the fraction of cost for gene therapy that resides in 
vector production. Dr. Anderson responded that the cost of producing the vector is 
probably 50% of the entire cost of the gene therapy procedure. The cost of producing 
the vector is substantial. 
Dr. McGarrity responded to the issue of cost. When current RCR testing procedures 
were compared to the standards used prior to the summer of 1992, GTI estimated an 
increase of about 7-fold in the staff time required for quality assurance assays based on 
the inclusion of co-cultivations and amplifications. If this increase is beneficial and cost 
effective, this money is well spent. He questioned Dr. Kahn on the 0.5% estimate she 
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Recombinant DNA Research, Volume 16 
