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Federal Register / Vol. 45, No. 227 / Friday, November 21, 1980 / Notices 
of eliminating pre-review of experiments 
by the IBCs until the frequency of 
principal investigator error in selecting 
the appropriate containment levels has 
been determined. 
The RAC voted 17 in favor, none 
opposed, with 1 abstention, that IBCs 
keep records of recombinant DNA 
research done in their institution, 
including a record of the frequency of 
errors in classificaion of experiments by 
the principal investigator. 
The RAC voted 15 in favor, 3 opposed, 
with no abstentions, that IBCs no longer 
need register with NIH recombinant 
DNA experiments for which 
containment levels are specified in the 
Guidelines. 
I accept these recommendations. 
The four-part motion passed by the 
RAC indicated the intent of the RAC to 
recomment acceptance of certain 
concepts in the proposal by Maxine 
Singer (i.e., elimination of the 
requirement for IBC registration with, 
and NIH review of, experiments for 
which the containment levels are 
specified in the Guidelines), but to defer 
recommendation of other concepts {i.e., 
the proposal to eliminate pre-review by 
the IBC for these experiments). 
As noted earlier, the proposal by 
Maxine Singer published as Item 8 in the 
Federal Register of August 21, 1980, 
consisted of proposed changes in many 
different places of the Guidelines, 
specified under subheadings "A” to “X”. 
Following the RAC meeting, I asked a 
four-person group to revise these 
proposed changes in order to translate 
the four-part general motion of the RAC 
into specific Guideline changes. The 
group (consisting of Dr. Bernard Talbot, 
my Special Assistant, Dr. William 
Gartland, Director of the Office of 
Recombinant DNA Activities, Dr. 
Maxine Singer, originator of the 
proposal, and Dr. Susan Gottesman, 
RAC member and originator of the four- 
part motion passed by the RAC) 
unanimously agreed on wording which 
translates the intent of the RAC into 
specific changes in the Guidelines. I 
have accepted their recommendations. 
The result is that some of the changes 
"A” through “X" originally proposed by 
Dr. Singer have been accepted as 
proposed; some have been rejected, 
thereby leaving the relevant portions of 
the Guidelines unchanged; and some 
have been further modified so that 
particular sections now are different 
from both the Guidelines prior to the 
Singer proposal and from the Singer 
proposal. 
Specifically, the sections where the 
changes proposed by Dr. Singer have 
been accepted are: "E” — Deletion of 
Section IV-C-3; “F* — Deletion of 
Sections IV-D-l-C and IV-D-l-C-(l) 
through IV-D-1-C{5); "G” — Deletion of 
Section IV-D-l-d; "H” — Amendment of 
Section IV-D-2-f; “I” — Amendment of 
Section IV-D-2-h; "K” — Amendment of 
Section IV-D-3-b; “L” — Amendment of 
Section IV-D-3-f; “P" — Amendment of 
Section IV-D-5-c-(3); "U”— Deletion of 
Section IV-E-3-b, IV-E-3-c-(l), IV-E-3- 
c — (2), and IV-E-3-c-(3); “V”— Deletion 
of Section IV-E— 4-a; and “W” — Deletion 
of Sections IV-F-1 and IV-F-2. 
The proposed changes which have 
been rejected thus leaving the 
Guidelines as they were previous to the 
Singer proposal are: “Q” — Heading of 
Section IV-D-5-d; “R” — Heading of 
Section IV-D-5-e; and "T" — Proposed 
deletion of Section IV— E— 1— b— (3)— (e). 
The proposed changes which have 
been farther modified so that the 
sections now read differently from the 
Guidelines prior to the Singer proposal 
and from the Singer proposal are: “A” — 
Section III; "B” — Section III-O; “C" — 
Last sentence of Section UI-A-3-a; 
"D” — Last sentence of Section III-A-3- 
b; “J” — Section IV-D-3-a; "M" — Section 
IV-D-5-a-(l); “N” — Section IV-D-5-b- 
(4); and “O” — Section IV-E-5-b-(5). 
In addition, Sections IV-F-3, IV-F-4, 
and VI-C, dealing with registration, 
have been eliminated, as has the 
proposed Section IV-D-5-e-(6). 
One consequence of these changes is 
that MUAs need no longer be filed with 
NIH and the term "MUA” has been 
deleted from the Guidelines. 
One part of the RAC four-part motion 
called for IBCs to keep records of 
recombinant DNA research done in their 
institution, including a record of the 
frequency of errors in classification of 
experiments by the principal 
investigator. This requirement for record 
keeping will be specified in the revision 
of the Administrative Practice 
Supplement to the NIH Guidelines to be 
issued in November 1980. 
During the RAC discussion, the 
concept of requiring the IBCs to report 
annually to NIH on all recombinant 
DNA research being done at the 
institution was rejected. NIH is 
sponsoring a meeting of IBC Chairmen 
on November 24-25, 1980. The issue of 
possibly reporting annually to NIH will 
be discussed at that meeting. Following 
that discussion, I will again review this 
issue. 
It should be emphasized that NIH 
remains responsible for specifying 
containment conditions for all 
experiments not explicitly covered by 
the Guidelines. This includes 
experiments requiring case-by-case 
review and exceptions to the provisions 
or prohibitions of the Guidelines. 
Principal investigators must petition 
NIH for consideration of such proposed 
experiments. NIH will follow existing 
procedures in such cases and will notify 
the principal investigators as before. No 
such experiments are to be approved by 
the IBCs until containment conditions 
have been set by the NIH. No such 
experiments are to be initiated by Pis 
until appropriate registration documents 
have been submitted to and approved 
by the IBC. The registration documents 
should include the NIH statement of 
containment conditions. 
XVII. Procedures For Review of Large- 
Scale Experiments 
Section I-D-6 of the Guidelines 
prohibits “large-scale experiments (e.g., 
more than 10 liters of culture) with 
organisms containing recombinant 
DNA's, unless the recombinant DNAs 
are rigorously characterized and the 
absence of harmful sequences 
established.” 
Section IV-E-l-b-(3)-(d) of the 
Guidelines states that the Director, NIH, 
is responsible for “authorizing under 
procedures specified by the RAC, large- 
scale experiments (i.e., more than 10 
liters of culture) for recombinant DNAs 
that are rigorously characterized and 
free of harmful sequences.” 
Part VI of the Guidelines, "Voluntary 
Compliance,” encourages institutions 
pot otherwise covered by the Guidelines 
to follow the standards and procedures 
set forth in the Guidelines. 
At its September 1979 meeting, the 
RAC adopted the following procedures 
to be followed by applicants proposing 
to exceed the 10-liter limit: 
"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. A specification of the total volume 
of the fermenter to be used. 
"d. Evidence that the recombinant 
DNAs to be employed in the research 
have been rigorously characterized and 
are free of harmful sequences. 
"e. A description of the applicant's 
laboratory practices, containment 
equipment, and facilities relevant to the 
containment of large volumes of culture. 
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