Recombinant DNA Advisory Committee - 12/3-4/92 
Presentation-Dr. Noguchi 
Dr. Murray called on Dr. Philip Noguchi to start the continued discussion on RCR 
assays. Dr. Noguchi commented on the FDA's standard for RCR testing. He explained 
that the important issue is the reason why these assays are performed. The FDA does 
not really expect that every investigator will be able to detect the absolute number of 
RCR in a defined volume, but the sensitivity of the assay does infer a measure of safety 
as demonstrated by current events. 
Experiments performed in Dr. Nienhuis' laboratory provided the first evidence that RCR 
have the capacity to cause disease. Recently, 3 consecutive lots of vector from a supplier 
demonstrated the presence of a recombinational event. These 2 incidents have assisted 
the FDA in quantifying the amount RCR that can produce pathology. Dr. Noguchi 
commended the report submitted by Dr. Anderson and stated that the report supplies 
the kind of information that the FDA welcomes. 
In regard to the supplier that produced 49 consecutive RCR-negative lots prior to 
experiencing an RCR-positive lot, Dr. Noguchi said that this occurrence indicated that 
the detection of RCR is not a cumulative experience, but a stochastic event. Therefore, 
every production lot must be viewed separately. Hazards are not always incompatible 
with treating patients. The critical issue is what are the risks associated with the 
administration of RCR into a patient. 
Dr. Noguchi explained two concepts employed at the FDA. First, there should be a 
master cell bank that is used as the gold standard for the testing of complex biological 
products. The assumption is that all of the cells within the master cell bank are 
identical. Second, the production bank, or the working cell bank, is obtained from cells 
that are cultured from the master cell bank. Testing of the working cell bank is different 
from the testing performed on the master cell bank. The master cell bank is assayed 
only once. 
Dr. Noguchi introduced Dr. Arifa Kahn of the FDA to present additional information 
regarding RCR testing requirements. 
Presentation-Dr. Kahn 
Dr. Kahn stated that given the present knowledge regarding the generation of RCR, one 
cannot rely on the theoretical probability of safety of any packaging cell system. Each 
system must be rigorously tested for the presence of RCR using the most sensitive assays, 
and must be demonstrated to be safe. 
Recombinant DNA Research, Volume 16 
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