23 
(1) What type of expedited procedure should be developed to deal with 
minor modifications of previously approved large-scale protocols 
and 
(2) What criteria should be appl ied to determine if a modification is 
indeed minor. 
She said she had not composed specific language to present to the RAC but 
wished to express her general thoughts, and hoped to obtain a sense of 
the Committee. She suggested that a formal subcommittee, or a working 
group, or several reviewers selected by ORDA, could evaluate the applica- 
tions to determine whether they involve minor modifications of an already 
approved proposal. If so, the package could be sent to the Director, NIH, 
for approval without review by the full RAC. She said the individuals 
responsible for the review would have two responsibilities: 
(1) To determine if the modification is indeed a minor modification. If 
one reviewer does not agree that the modification is minor, the pro- 
posal would be evaluated by the full RAC; 
(2) If the reviewers unanimously agree the modification is minor, the 
review group would determine whether the modification significantly 
affects any containment aspect of the parent proposal. She said the 
RAC might construct sane guidelines in this area, e.g., the general 
acceptability of deletions, single base changes, additions of short 
segments that do not lead to production of new products, change to 
an equivalent vector, etc. 
Dr. Gottesman said that while it would be extremely difficult in advance 
to imagine every possible change and its consequence, it will, in most 
cases, be obvious to the reviewers when a specific proposed modification 
is minor. She felt several RAC members involved in evaluating the ori- 
ginal parent proposal should be involved in review of any proposed minor 
modifications. After discussion of various aspects of the proposal, 
Dr. Gottesman agreed to formulate a specific proposal for consideration 
at the January 1981 meeting. 
XXI. REQUEST FOR CERTIFICATION OF HV1 BACILLUS SUBTILIS HOST-VECTOR SYSTEM 
Dr. Brill introduced a request (tabs 921, 931/5) from Dr. David B. Wilson, 
Cornell University. He said Dr. Wilson requests HV1 certification of a 
host-vector system based on certified host-components of HV1 Bacillus 
subtilis host-vector systems and a plasmid, pAB124, isolated from Bacillus 
stearothermophilus . Dr. Brill said Bacillus stearothermophilus is not a 
pathogen. He recommended that the plasmid be approved for use with certi- 
fied HV1 Bacillus subtilis hosts. 
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