Federal Register / Vol. 45, No. 227 / Friday, November 21, 1980 / Notices 
77379 
“f. Evidence of the applicant's or 
applicant institution's previous 
experience in handling large volumes of 
culture. Applicants should exhibit 
knowledge of state-of-the-art procedures 
for working with large volumes of 
microorganisms. 
“g. A description of procedures to be 
employed for the inactivation and 
disposal of large volumes of culture. 
“h. A description of procedures for 
containing and inactivating accidental 
spills, should they occur. 
“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. 
"These procedures may be refined or 
revised on the basis of discussion and 
action by the NIH Recombinant DNA 
Advisory Committee.” 
At recent RAC meetings, there have 
been extensive discussions of the role of 
the RAC and NIH in the review of large- 
scale proposals submitted by industry. 
(Minutes of RAC meetings are available 
from ORDA.) At the June 1980 meeting, 
the RAC passed a motion by a vote of 
seventeen to zero with one abstention 
that the following proposal be published 
in the Federal Register for consideration 
at the September 1980 meeting: 
"The following procedures should be 
adopted for approval of requests to grow 
greater than 10 liters of organisms 
containing recombinant DNA. The RAC 
will determine if a given recombinant 
DNA-containing strain is rigorously 
characterized and the absence of 
harmful sequences established. Such a 
determination shall include specification 
of the containment level (P-LS).. These 
determinations should not in any way 
be construed as RAC certification of 
safe laboratory procedures for industry 
scale-up. Adherence to the specified 
containment conditions is the 
responsibility of the local IBC." 
This proposal was published for 
comment in the Federal Register of 
August 21, 1980. There it was pointed 
out that if the proposal were accepted, it 
would have the effect of changing the 
application procedures to read as 
follows: 
“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 Memorandum of 
Understanding and Agreement (MUA) 
submitted to the local Institutional . 
Biosafety Committee. The MUA 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. 
“d. 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. 
“These procedures may be refined or 
revised on the basis of discussion and 
action by the NIH Recombinant DNA 
Advisory Committee.” 
During the comment period, two 
comments were received. 
One commentator stated: 
I regret that the RAC wishes to terminate 
its reviews of engineering plans for proposed 
private-sector DNA operations. 
Another letter stated: 
We agree with the RAC proposal passed in 
June 1980, to exclude regulatory functions 
dealing with industrial scale-up. We believe 
that the current mission of the RAC is 
appropriate and that its present constitution, 
representing scientific and public interests, is 
not well suited for a regulatory role. Other 
bodies of the federal government already 
have the mandate to carry out regulatory 
functions and should acquire necessary 
resources and expertise. 
The proposal was discussed at length 
at the September 25-26, 1980 RAC 
meeting. 
Dr. Krimsky said that although at 
previous RAC meetings he had argued 
strongly for proposals like this, he had 
now changed his mind, because he had 
come to realize that such pre-review as 
the RAC has been performing is unique, 
and that no other agency would conduct 
such a review. He proposed, as an 
alternative proposal, that there be 
established a subcommittee of the RAC 
made up of some members of the RAC 
and some members of NIH staff with 
expertise in facilities and technologies, 
and that the subcommittee request 
representation from the Occupational 
Safety and Health Administration 
(OSHA), the National Institute for 
Occupational Safety and Health 
(NIOSH), the Center for Disease Control 
(CDC), and the Environmental 
Protection Agency (EPA). In this 
proposal, the subcommittee would 
review engineering and technology, and 
its review would be transmitted directly 
to the Director, NIH. After discussion, 
this alternative motion was withdrawn 
from consideration for the time being, 
with the understanding that it would be 
reconsidered later in the meeting. 
During further discussion of the 
proposal as published in the Federal 
Register of August 21, 1980, Dr. Fedoroff 
indicated her support for eliminating 
RAC review of the details of physical 
containment for individual large-scle 
proposals, as is already the case for 
small-scale research. Dr. King indicated 
her support of the proposal as an 
acceptable compromise. 
Following further discussion, the RAC 
voted 12 in favor, 5 opposed, with one 
abstention, to adopt the proposal as 
published in the Federal Register of 
August 21, 1980. 1 accept this 
recommendation and procedures for its 
implementation are published at the end 
of this section. 
Later in the meeting, Dr. Krimsky 
introduced the following motion to 
establish a large-scale review 
subcommittee: 
“An industrial review subcommittee 
of the RAC shall be established with the 
responsibility for advising the Director 
on procedures and facilities design 
pertaining to applications for large-scale 
operations. 
"After the full RAC has reviewed the 
biological containment requirements for 
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