Recombinant DNA Advisory Committee - 7/31/90 
modifications that did not necessarily have implications for the 
gene therapy portion of the procedure also had to come back 
through the RAC, or whether this is delegated to the IRBs and the 
FDA. Dr. McGarrity said he believed that protocols are approved 
as submitted. If any significant changes are to be made, they 
would have to be reviewed again. This proposed amendment is only 
to facilitate approval of minor modifications and changes. 
Dr. Epstein said he thought that only changes that were in the 
purview of the RAC would have to come back before it. The local 
IRB may sign off on any internal things which do not need to come 
back before the RAC. Dr. McGarrity asked Dr. Parkman to comment 
on this. 
Dr. Parkman said the present understanding is that if one has an 
approved protocol and one wishes to make a change in that 
protocol, i.e., the issue of intravenous versus intraperitoneal 
administration of cells, there should be legitimate reasons for 
why this change should occur. It should first go to the local 
IRB for approval and then be forwarded to the HGTS and the RAC. 
He said he viewed the protocols as being approved in total and 
that decisions made by the local IRB would weigh heavily on the 
determination of whether something was a major or minor 
modification. 
Dr. R. Murray moved adoption of the proposed change to the 
"Points to Consider," as amended by himself and Mr. Brewer. Mr. 
Brewer said he did not want to append specific wording to the 
document as proposed. However, he felt it should be viewed as a 
"rule of construction," that the criteria should define a minor 
modification as one that does not knowingly and unreasonably 
increase risk. This would allow the Chair to have some 
flexibility and latitude and not be bound by precise language 
which cannot be met. Mr. Brewer seconded Dr. R. Murray's motion. 
Dr. Post asked a procedural question. Since the RAC's function 
is advisory in nature to the Director of NIH, do these kinds of 
changes have to go beyond the Chairs of the HGTS and the RAC for 
approval? Dr. Wivel said this was not the case. 
Dr. Childress said he felt the wording of Dr. R. Murray's 
amendment to the proposed change should be changed since it is 
assumed that the Chairs can consult with whomever they wish. He 
suggested the wording of the sentence be: 
"It is expected that the Chairs will consult with 
appropriate members of the committee." 
Dr. R. Murray agreed, saying this was a diplomatic way to state 
the expectation of the committee in this regard, and he accepted 
Recombinant DNA Research, Volume 14 
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