Recombinant DNA Advisory Committee- 9/12-13/94 
Dr. Mclvor addressed questions regarding RCR assays. RCR was assayed by a marker 
virus rescue assay. In his assay, upon infection by RCR, a virus containing the neo R 
marker gene will be rescued. Using the assay, no RCR has been detected in aliquots of 5 
ml supernatants from the L2SN producer cells. No S + L‘ assay has been performed yet. In 
the future, every vector production lot and master cell bank will be assayed. 
Dr. Parkman asked if the RAC criterion of less than 1 RCR per 100 ml patient dose will 
be applied. Dr. Mclvor said it has been planned to screen larger volumes of the 
supernatants. But he noted the FDA requirement is to screen for 5% of the production 
lot, i.e., 500 ml for a 10 liter lot. Dr. Whitley indicated that this kind of screening effort is 
excessive and expensive. 
Ms. Meyers asked Dr. Noguchi from FDA to comment on this issue. Dr. Noguchi said 
that stringent requirement for RCR testing is a result of the primate studies that show that 
RCR can cause malignant lymphoma. It is the purpose of FDA’s public meetings to 
encourage investigators and sponsoring companies to discuss these RCR testing 
requirements. There is not enough data to suggest which levels of testing are adequate. 
Lacking reliable safety data to suggest which level of testings such as 5%, 1%, or 0.5% of 
a production lot is adequate, FDA’s position as a responsible body is to take a 
conservative stand. 
Dr. Mclvor commented that the amplification assay for RCR required by FDA is very 
costly, around $10,000 per specimen. The marker virus rescue assay is used in most 
research laboratory, but not for vector production. Dr. Mclvor said that he is planning to 
do the S *L~ assays for replication competent amphotropic virus. Dr. Noguchi emphasized 
that there is no inherent reason not to use the marker rescue assay if it can detect RCR to 
some degree of certainty. 
Mr. Capron commented that RCR is more of a concern for children who have a long life 
span with a mild disease. Dr. Mclvor said the question is how far does one have to go in 
sensitivity level in order to ensure that the research subjects are being given a safe stock. 
Ms. Meyers said that for research that is sponsored by commercial companies, there is less 
problem. But the cost is prohibitive for protocol like this one which does not have a 
commercial sponsor. Mr. Capron said that if the research is promising, it should be 
funded at an adequate level rather than cut the safety standard, and run the risk of 
harming people. 
Dr. Mclvor said the standard has not been established. Dr. Noguchi agreed it needs to be 
established. Ms. Meyers said there should be special federal funds for this type of project. 
Dr. Parkman said that clinical research has risks. Is there is a moral imperative to reduce 
the risks to as close to zero, disregarding the costs of doing the tests? Dr. Parkman asked 
if the marker rescue assay is much cheaper than the amplification test, would the RAC 
accept an assay with an error rate of 50% with the understanding that it can save 90% of 
the money. Ms. Meyers answered that she would not. Dr. Parkman said that if this 
information is disclosed in the Informed Consent document to the patients, would it be 
acceptable? 
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Recombinant DNA Research, Volume 20 
