Federal Register f VoL 58, No. 199 / Monday, October 18, 1993 / Notices 
53819 
“As noted In the subsection of Section 
IV-C-l-b-(l). the Director, NIH, may 
take certain actions with regard to the 
Guidelines after the issues have been 
considered by the RAC An updated list 
of these actions are available from the 
Office of Recombinant DMA Activities, 
National Institutes of Health, Building 
31, Room 4B11, Bethesda, Maryland 
20892.“ 
G. Amendment to the Guidelines for the 
Submission of Human Gene Transfer/ 
Therapy Protocols for Review by the 
RAC of the Points to Consider/NIH 
Guidelines 
The Title and Section I of the 
Guidelines for the Submission of 
Human Gene Transfer /Therapy 
Protocols for Review by the RAC 
(Federal Register. February 18, 1993, 
page 9104) will read as follows: 
“ Guidelines far the Submission of 
Human Gene Transfer Protocols for 
Review by the Recombinant DNA 
Advisory Committee 
“L Investigator Submitted Material: 
"Written proposals must be submitted 
in the following order: (1) Scientific 
abstract — 1 page; (2) non-technical 
abstract — 1 page; (3) Institutional 
Biosafety Committee and Institutional 
Review Board approvals; (4} Points to 
Consider — 5 pages; (6) protocol — 20 
pages excluding appendices; (7) 
Informed Consent Document — approved 
by the Institutional Review Board; (8) 
appendices including tables, figures, 
and manuscripts; and (9) Curricula 
vitae — 2 pages in Biographical sketch 
format When a proposal has been 
submitted previously, there should be a 
short section (5200 words) immediately 
following the abstracts that summarizes 
the major revisions since the last 
review. Data provided * * *. 
**• * • written responses (including 
critical data in response to the primary 
reviewers' comments) must be 
submitted by the Principal Investigators 
to the Office of Recombinant DNA 
Activities 22 weeks before the RAC 
meeting. ' 
“Oral Responses to the RAC Principal 
Investigators must limit their oral 
responses to the RAC only to those 
questions that are raised during the 
meeting. 
Oral presentations of previously 
submitted material and/or critical data 
that was not submitted 22 weeks prior 
to the RAC meeting is prohibited.’* 
H. Amendments to Sections ID, IV. V 
and Appendix C and F of the NIH 
Guidelines Regarding the Cloning of 
Toxin Molecules 
Sections ID, IV, and V, and 
Appendices C and F will be amended as 
follows: 
“Section ED. Guidelines for Covered 
Experiments. 
“Part ID discusses experiments 
involving recombinant DNA. These 
experiments have been divided into five 
classes: 
“ID-A. Experiments which require 
specific RAC review and NIH and IBC 
approval before initiation of the 
experiment; 
“ID-B. Experiments which require 
NIH (Office of Recombinant DNA 
Activities/ORDA) and Institutional 
Biosafety Committee (IBQ approval 
before initiation of the experiment; 
*TD-G Experiments which require 
IBC approval before initiation of the 
experiment; 
“II1-D. Experiments which require 
IBC notification at the time of the 
experiment; 
“ffl-E. Experiments which are exempt 
from the procedures of the Guidelines, 
"IF AN EXPERIMENT FALLS INTO 
BOTH CLASS Bk-A AND ONE OF THE 
OTHER CLASSES, THE RULES 
PERTAINING TO CLASS IH-A MUST 
BE FOLLOWED. If an experiment falls 
Into Class III-E and into either Class EB— 
C or IH-D as well, it can be considered 
exempt from the requirements of the 
Guidelines. Changes * * * ** 
Section IB-A-I will be moved to a 
new Section IH-B-1. New Section ID-B 
will read: 
“Section EJ-B-Experiments That 
Require NIH (ORDA) and IBC Approval 
Before Initiation. 
“Section IU-B-1. Deliberate formation 
of recombinant DNA containing genes 
for the biosynthesis of toxin molecules 
lethal for vertebrates at an LD*> of less 
than 100 nanograms per kilogram body 
weight • • • 
“Section IE-B-l-(a). Experiments hi 
this category cannot be initiated without 
submission of relevant information an 
the proposed experiment to NIH 
through ORDA. The containment 
conditions for such experiments will be 
determined by ORDA in consultation 
with ad hoc experts. Such experiments 
also require the approval of the IBC 
before initiation (see Section IV-Ol-b- 
(3H0/‘ 
Sections IB-A-2, EJ-^A-3, m-A-4 
will be renumbered to EI-A-1, IB-A-2, 
Ett-A-3 respectively. Sections ID-B, IB- 
C, ID-D will be renumbered to IB-C, IB— 
D, and IB-E respectively. 
The new Section IB-C-2 will read: 
"Section IB-C-2. Experiments in 
Which DNA From Human or Animal 
Pathogens (Class 2, Class 3, Class 4, or 
Class 5 Agents (l)) Is Cloned In 
Nonpathogenic Prokaryotic or Lower 
Eukaryotic Host-Vector Systems. 
"Section DJ-C-2-e. * * * Many 
experiments in this category are exempt 
from the Guidelines (see Section IB-E- 
4) and BI-E-6). Experiments involving 
the formation of recombinant DNA for 
certain genes coding for molecules toxic 
for vertebrates require NIH (ORDA) 
approval (see Section IB-B-1) or must 
be carried out under NIH specified 
conditions as described in Appendix P. M 
Section IV-B— 5-b-(3) will read: 
"Section IV-B— 5-b-{3). Petition NIH 
(ORDA), with concurrence of the IBC for 
approval to conduct experiments 
specified in Sections IB-A and Bt-B of 
the Guidelines;** 
Section rV-C-*-b-(3H0 wiH be 
deleted which reads: "Approving the 
cloning of toxin genes in host-vector 
systems other than E coll K-1Z (see 
Appendix F); and" 
Section IV-C-1— b-(3Hg) will become 
the new Section IV-C-l-b-(3)-(f). 
The new Section, IV-C-3-a will read: 
"Reviewing and approving 
experiments involving the cloning of 
genes encoding for toxin molecules that 
are lethal for vertebrates at an LD*> 5100 
nanograms per kilogram body weight in 
organisms other then E coli K— 12 (see 
Section IB-B-1 and Appendices F-I and 
F-E)." 
Sections IV-C-3-a and IY-C-3-b will 
be renumbered to become Sections IV- 
C-3-b and IV-G-3-c respectively. 
Section V-2 will read: 
"* * * In the cases falling under 
Sections IB-A through IB-D, this 
judgment is to be reviewed and 
approved by the IBC * * •** 
Appendix C will read: 
"Appendix C. Exemptions Under 
Section IB-D-5. 
"• * * Appendix C-L Recombinant 
DNA in Tissue Culture * * * 
“• * * Exceptions. The following 
categories are not exempt from the NIH 
Guidelines: (1) experiments described in 
Section IB-A which require specific 
RAC review and NIH and IBC approval 
before initiation, (ii) experiments 
described in Section ID-B which require 
NIH (ORDA) and IBC approval before 
initiation, (iii) experiments involving 
DNA from Class 3, 4, or 5 organisms (1) 
or cells known to be infected with these 
agents, and (iv) experiments involving 
the cloning of toxin molecule genes in 
E coli K-12 (see Appendix F). 
"* * * Appendix C-IL Experiments 
Involving E coli K-12 Host-Vector 
Systems • * * 
“* * * Exceptions. The following 
categories are not exempt from the NIH 
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