Recombinant DNA Advisory Committee - 12/3-4/92 
the safety to the patient and the ability of the vector supplier to perform the helper vims 
assays. There are physical and financial limitations to RCR testing, e.g., if the supplier is 
required to culture 20,000 dishes of cells, this requirement will introduce a practical 
impossibility to the testing process. The question is where do you draw the line? Risk 
versus benefit has to be weighed in establishing RCR testing criteria. 
Review-Dr. Geiduschek 
Dr. Geiduschek stated that it was his expectation that this report would outline specific 
proposed improvements in the testing for RCR. However, the report was a redefinition 
of the problems associated with these assays. The certification of retrovirus vector lots 
can be greatly improved, and these improvements are necessary. With improved testing, 
currently generated materials can be demonstrated to be free of RCR contamination in 
ways not possible by current methods. It is preferable to refine these analytical methods 
rather than to relax the testing criteria. The RCR report should be deferred for 
revisions, and it could be reconsidered at the next RAC meeting. 
Dr. Geiduschek noted that the report makes a specific claim about the margin of safety 
that is based on an argument that is not correct. The calculations are probably off by 
several logs. In addition, he was not in agreement with the reported number of RCR 
that are detectable by current assays. The report suggests that the conventional S + L* 
assay has an efficiency considerably less than 1, probably less than 0.1, when performed 
in the presence of a large quantity of RCR. Therefore, the standard S + L' assay should 
be abandoned in favor of the one of the amplification assays. He stated that he was 
disappointed that no new data was accumulated in the last 6 months with regard to the 
development of improved assays. This issue was originally discussed at the June 1992 
RAC meeting. In particular, co-cultivation assays could have been brought to the 
evaluation stage based on the data that was presented at the June meeting. 
Dr. Geiduschek said that he was discouraged that there has been no incentive to 
generate a more absolute measure of quality assurance. The report was presented in 
terms of the global experience of one vector supplier. How would this data generate 
quality assurance for a new provider? The report states that the material supplied by 
this one company has had no evidence of RCR contamination in 147 lots. Since this 
report was submitted, RCR contamination has occurred. However, there is reassurance 
in the fact that the contamination was detected by current testing methods. 
Review--Mr. Barton 
Mr. Barton stated that most of his comments had been covered thoroughly in Dr. 
Geiduschek's review. He reminded the RAC that they should consider the importance 
of maintaining consistency in risk and safety assessment among different kinds of vectors 
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Recombinant DNA Research, Volume 16 
