Recombinant DMA Advisory Committee - 3/3-4/94 
from Major to Minor Actions', and in the future, possibly to the registration category. Dr. 
Straus suggested a minor change to the flow chart describing the review process 
regarding reporting these actions to the next RAC meeting by the Chair. Dr. Parkman 
said that the NIH Director will have to make the decision to delegate authority to the 
RAC to approve Minor Actions. Dr. Wivel stated that a Minor Action is different from 
the single patient Expedited Review category, which requires approval from the NIH 
Director. All human experiments involving recombinant DNA will be tracked by the 
RAC except those vaccine studies that are considered exempt under Footnote 21 of the 
NIH Guidelines. Dr. Smith asked whether the Minor Actions will require IBC and IRB 
approvals prior to submission to ORDA Dr. Parkman said that prior local approvals 
will be a condition for submission to ORDA 
Committee Motion-Minor Action 
The RAC approved a motion made by Dr. Carmen and seconded by Dr. Straus to accept 
the amendments to the NIH Guidelines and the Points to Consider by a vote of 13 in 
favor, 0 opposed, and no abstentions. The proposed amendments will: (1) establish an 
Accelerated Review process (Minor Actions) for certain categories of human gene transfer 
experiments, (2) allow NIH/ORDA to assign the appropriate review category to all 
human gene transfer proposals that are submitted in compliance with the NIH 
Guidelines, and (3) allow NIH/ORDA to approve those categories of human gene 
transfer experiments that qualify as Minor Actions in consultation with the RAC Chair 
and one or more RAC members, as necessary. At their discretion, the RAC Chair 
and/or NIH/ORDA may determine that any proposal shall require review by the full 
RAC (Major Action). 
Proposed Categories (Minor Actions)-Dr. Parkman 
Dr. Parkman presented a draft document entitled: Proposed Categories for Minor Actions 
to the NIH Guidelines Involving Human Subjects. The proposed categories are 
considered guidelines for consideration and are not intended as a set of fixed categories. 
The proposed categories of Minor Actions are: (1) vaccines that are not considered 
exempt under Footnote 21, (2) lethally irradiated tumor cells/no replication-competent 
virus, (3) additional sites, (4) new Principal Investigator/new site, (5) "umbrella" 
protocols, (6) modifications not related to gene transfer, and (7) gene marking protocols. 
The risk/benefit ratio will be applied to each individual protocol. Dr. Parkman 
described a hypothetical protocol in which irradiated retinoblastoma cells genetically 
modified to produce IL-2 will be administered to a child's eye. Although this experiment 
would be encompassed by the lethally irradiated tumor cell category, the serious clinical 
setting represents an increased risk/benefit ratio that would require an increased level of 
review, i.e.. Major Action. However, the majority of experiments proposed under this 
category would qualify as Minor Actions. Dr. Wivel cited an example of injecting a 
plasmid DNA vector to a subcutaneous tumor mass vs. administering the vector DNA 
through a catheter to a lung metastasis. Dr. Parkman said that a protocol such as 
subcutaneous administration of irradiated cells producing IL-2 to a new tumor type such 
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