Recombinant DNA Advisory Committee - 12/3-4/92 
Dr. D. Miller asked Dr. Anderson about the current cost of certifying a vector for human 
use? Dr. Anderson asked Dr. Gerard McGarrity of GTI to respond to Dr. D. Miller's 
question. Dr. McGarrity stated that the entire cost is approximately $100,000. If the 
cost of vector certification increases, these expenditures would be prohibitive to small 
start-up companies. 
Dr. Post asked Dr. Anderson to describe the assay(s) that were performed that detected 
the breakout that occurred in one of the vector lots? Dr. Anderson responded that the 
breakout was detected by the standard S + L‘ assay and confirmed with NIH 3T3 
amplification. 
Dr. Noguchi reminded Dr. Anderson that there is data that is available, only to the 
FDA, that indicates that it is reasonable to consider additional testing. Dr. Anderson 
asked if these findings were demonstrated on a supernatant assay. Dr. Noguchi stated 
that he could not discuss the data. Dr. Anderson said that these data were derived from 
supernatant assays. 
Dr. Anderson said that if co-cultivation proves to be twice a sensitive as current methods, 
but costs 10 times as much, what is the end result? Dr. Noguchi said that it is 
reasonable to discuss this issue, and that the FDA will work with investigators to develop 
reasonable recommendations. 
Dr. Parkman said that there is a basic problem with the FDA's proposal to test an 
aliquot, because there will always be the possibility that your aliquot does not contain a 
vector-producing cell. There will always be a degree of uncertainty that you have missed 
by selection up front, the agent you are trying to detect. Dr. D. Miller reminded Dr. 
Parkman that testing an entire lot assures that there is zero contamination. Is it really 
necessary to ensure zero contamination? Culturing the entire production lot for a month 
is unworkable in terms of cost and unreasonable in terms of risk. At some point, the 
RAC and FDA have to decide on an acceptable level of contamination. 
Dr. D. Miller said that at this point, decisions can only be made based on current data. 
If more informative data is verified, then present criteria may have to be modified. 
Current data, however, suggests that the established testing criteria are sufficient. 
Dr. Kahn stated that the proposed testing procedures developed by the FDA were 
established for the purpose of simplification, as well as adding a sensitivity factor. The 
draft proposal is not intended to complicate testing procedures or increase costs. As a 
point of clarification, investigators would not be required to perform all of the assays 
that are listed for the detection of RCR. Any one of these assays is sufficient to detect 
retrovirus. GTI is already performing S + L' and PCR assays. The immunofluorescence 
assay is suggested as an alternative, because it can detect all four classes of retroviruses. 
Recombinant DNA Research, Volume 16 
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