Recombinant DMA Advisory Committee - 3/3-4/94 
as prostate cancer would qualify for Accelerated Review. 
Dr. Secundy and Ms. Grossman suggested that the working group define the criteria for 
Minor Actions to avoid arbitrary decisions. Dr. Parkman explained that establishing very 
rigid criteria would exclude a large number of proposals. 
The RAC discussed the types of experiments that would be considered under the lethally 
irradiated tumor cell category. Dr. Parkman said that there are several possible options 
under this category: (1) a RAC-approved vector with an approved gene insert, (2) a 
RAC-approved vector with a new gene insert, (3) a modified RAC-approved vector, (4) a 
new tumor type, and (5) a new route of irradiated tumor cell administration. There 
should be no replication competent vims. 
The RAC considered previously approved proposals initiated at new sites and/or by new 
Principal Investigators. Dr. Straus and Ms. Grossman expressed their concern that new 
investigators may not possess adequate qualifications to conduct a duplicate study, and 
that such a situation may pose increased risk to the patients or the environment. Dr. 
Motulsky agreed that adequate qualifications is a major issue. Drs. Post, Parkman, and 
DeLeon assured the RAC that any proposal that presents such concerns can be elevated 
to the next full level of review, i.e.. Major Actions. 
Dr. Wivel raised a question regarding quality control in umbrella protocols. Would a 
single Principal Investigator be responsible for all study sites or a different Principal 
Investigator for each site? Dr. Parkman explained that the RAC-approved Herpes 
simplex vims thymidine kinase/Ganciclovir protocols to treat brain tumors are an 
example of studies that may qualify for Accelerated Review. The vector producing cells 
are prepared at a central facility and distributed to each site for administration to the 
patients by neurosurgeons; recombinant DNA expertise is not required in such a 
situation. Dr. Straus said that local expertise may be required at each site to perform 
assays such as examining the persistence of vector sequences in patients and assuring that 
these biological agents are not inadvertently released to the environment. Ms. Grossman 
agreed that issue is important. Dr. DeLeon said that competence of the Principal 
Investigator at each site will be a question for review. Dr. Post said that these are issues 
to be considered when the protocol is submitted for Accelerated Review and the RAC 
does not have to decide at this time. 
With regard to protocols involving lethally irradiated tumor cells. Dr. Post said that such 
studies should be limited to RAC-approved vectors. Dr. Merchant asked whether direct 
in vivo administration of a vector to the tumor site would be considered a Minor Action. 
Dr. Parkman said that if the proposal represents any substantial change over a previously 
approved study, the experiment would be reviewed as a Major Action. Dr. Carmen asked 
whether the RAC-approved vector/new gene insert category includes any cDNA insert. 
Dr. Carmen expressed his concern regarding blanket inclusion of any cDNA insert even 
if the tumor cells are lethally irradiated. Dr. Parkman said that ORDA should review 
each proposal independently since certain cDNA inserts may pose risk, e.g., insertion of 
cDNA encoding for a toxin gene. Drs. Post, Straus, Secundy, and Ms. Grossman 
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Recombinant DNA Research, Volume 19 
