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Federal Register / Vol. 45, No. 227 / Friday, November 21, 1980 / Notices 
a large-scale proposal, the subcommittee 
shall examine the applicant’s plans for 
large-scale operations and issue 
recommendations to the Director on 
plant design, health surveillance and 
environmental monitoring. The Director 
shall advise institutions of 
recommended design parameters and 
operational procedures. The 
determination shall not be construed as 
NIH certification of industrial 
operations. 
“The subcommittee shall invite 
participation from NIH’s biosafety staff 
plus OSHA, NIOSH, CDC, FDA, EPA, 
and USDA." 
Dr. Fedoroff expressed concern about 
delays if first the full RAC and then 
subsequently a subcommittee were to be 
involved in the review process. Others 
agreed. Dr. Gottesman said that she was 
opposed to continuation of review of 
equipment design in individual 
applications by either the full RAC or 
subcommittee. Dr. Logan of OSHA, 
speaking in behalf of the proposal, said 
that the delays need not be serious and 
that such subcommittee review would 
be beneficial. He said that OSHA does 
not have the legal authority to conduct 
pre-review of applications. Dr. Campbell 
said that while he opposed a 
subcommittee doing pre-review of 
individual applications, he favored a 
subcommittee to prepare future 
revisions of the Physical Containment 
Recommendations for Large-Scale Uses 
of Organisms Containing Recombinant 
DNA Molecules (i.e., the definitions of 
Pl-LS, etc.) and to monitor how well the 
system is working. Dr. Gottesman 
proposed an amendment to Dr. 
Krimsky’s motion to establish the 
subcommittee with these functions, but 
to do no pre-review of individual 
applications. An amendment to this 
amendment proposed by Dr. Krimsky to 
include subcommittee pre-review of 
individual applications failed by a vote 
of 3 in favor, 15 opposed, with no 
abstentions. After further amendments 
were adopted, the RAC passed the 
following motion by a vote of 15 in 
favor, 2 opposed, with 1 abstention: 
"A large-scale review subcommittee 
of the RAC shall be established with the 
responsibility for advising the RAC on 
procedures and facilities design 
pertaining to large-scale operations, and 
on the performance of local IBCs in 
reviewing physical containment 
facilities. 
“The subcommittee shall invite 
participation from NIH’s biosafety staff 
plus OSHA, NIOSH, CDC, FDA, EPA, 
and USDA.” 
I agree with the establishment of a 
group to report to the RAC on 
recommendations for future revisions of 
the Physical Containment 
Recommendations for Large-Scale Uses 
of Organisms Containing Recombinant 
DNA Molecules (i.e., the definitions of 
Pl-LS. etc.) and on the performance of 
local IBCs in reviewing large-scale 
physical containment facilities. A 
Working Group of the RAC was 
established at the May 1979 meeting to 
develop the Physical Containment 
Recommendations for Large-Scale Uses 
of Organisms Containing Recombinant 
DNA Molecules. These 
recommendations were reviewed at the 
December 1979 and March 1980 RAC 
Meetings before being published in the 
Federal Register on April 11, 1980. 
Establishing a new “subcommittee” of 
the RAC to deal with this issue would 
require a formal change in the RAC 
Charter. Therefore, I favor reconstitution 
of the current RAC “Working Group” for 
this purpose. As noted above (see item 
IV of this announcement), the RAC has 
recommended that RAC “members 
should be chosen to provide expertise in 
fermentation technology, engineering, 
and other aspects of large-scale 
production.” I expect that an individual 
with these qualifications will shortly be 
appointed. When this happens, I will 
ask that the appointee consult with the 
RAC Chairman and that together they 
decide on which additional RAC 
members should be appointed to the 
reconstituted Large-Scale Review 
Working Group. The RAC recommended 
that participation be invited from “NIH’s 
biosafety staff plus OSHA, NIOSH, 
CDC, FDA, EPA, and USDA.” Ideally, all 
Federal agencies with representatives 
on the RAC should be invited to 
participate in the deliberations of the 
Working Group. 
In accordance with the 
recommendation of the RAC, the 
Working Group will not be involved in 
pre-review of individual applications. To 
assist in its function of advising the RAC 
on the performance of local IBCs in 
reviewing physical containment 
facilities and on future revisions of the 
Large-Scale Physical Containment 
Recommendations, the Working Group 
may request information from individual 
companies. Since NIH is not a 
regulatory agency, the intent of any such 
information collection will be fact- 
finding, to help in development of 
general recommendations from the 
Working Group to the RAC, and not for 
purposes of regulatory actions directed 
at individual companies. 
In response to recommendations of 
the RAC, the revised application 
procedures for large-scale proposals are 
now promulgated as final, i.e.: 
I 
“Application Procedures for Large- 
Scale Recombinant DNA Experiments. 
"1. For each research project 
proposing to exceed the 10-liter limit, the 
applicant shall file a request with the 
NIH Office of Recombinant DNA 
Activities (ORDA). The request should 
include the following information: 
"a. The registration document 
submitted to the local Institutional 
Biosafety Committee. This should 
include, or have appended to it, a 
summary paragraph which describes the 
proposed project in language that is 
comprehensible to non-specialists. 
“b. A statement of the rationale for 
wishing to exceed the 10-liter limit. 
“c. Evidence that the recombinant 
DNAs to be employed in the research 
have been rigorously characterized and 
are free of harmful sequences. 
‘id. Specification of the P-LS level 
proposed to be used as defined in the 
NIH Physical Containment 
Recommendations for Large-Scale Uses 
of Organisms Containing Recombinant 
DNA Molecules. (Federal Register, April 
11, 1980). 
“2. Each request submitted to ORDA 
shall be referred to a working group of 
the NIH Recombinant DNA Advisory 
Committee for review. 
“3. Following review and approval by 
the working group, each request shall be 
submitted to the entire Recombinant 
DNA Advisory Committee for review. 
“4. Following review and approval by 
the RAC, each request shall be 
submitted to the Director, NIH, for final 
review. 
“5. Applications for large-scale 
experiments which are submitted by 
institutions not receiving NIH funds for 
recombinant DNA research shall be kept 
confidential (provided the institutions so 
desire) in accordance with the 
provisions of the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules and to the extent permitted 
by law. 
“These procedures may be refined or 
revised on the basis of discussion and 
action by the NIH Recombinant DNA 
Advisory Committee.” • 
These application procedures are 
identical to those published for comment 
on August 21, 1980, except for the 
elimination of the term “Memorandum 
of Understanding and Agreement," its 
replacement by the term “registration 
document,” and addition of the clause 
"and to the extent permitted by law” in 
paragraph 5. As discussed above (in 
item XVI of this announcement), the 
term “Memorandum of Understanding 
and Agreement” has been eliminated 
from the Guidelines. The revised 
Guidelines, in Section III, describe the 
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