67i»4 
Federal Register / VoL 59, No. 29 / Friday, February 11, 1994 / Notices 
XL Amendments to Sections I, in, IV, 
and V of the NIH Guidelines and the 
Points to Consider in the Design and 
Submission of Protocols for the 
Transfer of Recombinant DNA into the 
Genome of Human Subjects (Points to 
Consider) Regarding NIH (ORDA) 
Review and Approval of Certain 
Categories of Human Gene Transfer 
Experiments That Qualify for the 
Accelerated Review Process 
"Dr. Robertson Parkman, Chair of the 
Working Group on Accelerated Review 
Protocols, will present an overview of 
the proposed amendments to the NIH 
Guidelines and the Points to Consider. 
The proposed amendments will: (1) 
Establish an accelerated review process 
for certain categories of h\nnan gene 
transfer experiments (i.e., “umbrella" 
multiple site protocols in which the 
Principal Investigator is responsible for 
the quality control and data reporting 
for research conducted at all sites, and 
duplicate protocols conducted at sites 
other than those cniginally approved by 
the RAC and in which there is a new 
Principal Investigator). (2) allow the 
National Institutes of Health (Office of 
Recombinant DNA Activities) to assign 
the appropriate review category to all 
human gene transfer prop>osals that are 
submitted in compliance with the NIH 
Guidelines. (3) allow the National 
Institutes of Health (Office of 
Recombinant DNA Activities) to 
approve those categories of human gene 
transfer experiments that qualify for the 
accelerated review process in 
consultation with the Chair and one or 
more RAC members, as necessary, and 
(4) exempt certain experiments 
involving the transfer of recombinant 
DNA or DNA or RNA derived from 
recombinant DNA into one or more 
human subjects which are not covered 
by Footnote 21. All human gene transfer 
experiments approved by the National 
Institutes of Health (Office of 
Recombinant DNA Activities) through 
the accelerated review process will be 
provided in a report by the RAC Chair 
at the next regularly RAC meeting and 
will be included in the list of approved 
experiments which is available from the 
Office of Recombinant DNA Activities, 
Building 31, room 4B11, Bethesda, 
Maryland 20892. The RAC recommends 
that these amendments be published in 
the Federal Register for public comment 
and review by tlie full RAC during its 
March 2-3, 1994, meeting. The 
proposed amendments to the NIH 
Guidelines are as follows: 
"Section L Scope of the NIH Guidelines" 
"Section I-A. Purpose" 
(No Changes! "The purpose of the NIH 
Guidelines is to sp>ecify practices for 
constructing and handling; (i) recombinant 
DNA molecules, and (ii) organisms and 
viruses containing recombinant DNA 
molecules.” 
(No ChangesI "Any recombinant DNA 
experiment, which according to the NIH 
Guidelines requires approval by the NIH, 
must be submitted to the NIH or to another 
Federal agency that has jurisdiction for 
reriew and approval Onoe approval, or other 
applicable clearances, are obtained from a 
Federal agency other than the NIH (whether 
the expreriment is referred to that agency by 
the NIH, or sent directly there by the 
submitter), the experiment may proceed 
without the necessity for NTH review or 
approval.” 
(Amended) “Certain experiments that 
involve the deliberate transfer of recombinant 
DNA or DNA or RNA derived from 
recombinant DNA into one or more human 
subjects (see Footnote 21) shall be considered 
Major Actions to the NiH Guidelines (see 
Section lV-C-l-b-{l)-(d)), and shall require 
RAC review and NIH Director approval, if 
determined by NIH (ORDA) In consultation 
with the RAC Chair and/or one or more RAC 
members, as necessary, to: (i) Represent 
novel characteristics (e^., target disease or 
vector), (ii) represent an uncertain degree of 
risk to human health or the environment, or 
(iii) contain information determined to 
require further public review (see Section K- 
A-3)." 
(Addition) "Experiments involving the 
transfer of recombinant DNA to one or more 
human subjects that are not considered under 
Section ni-A-3 may qualify for Accelerated 
Review (see Section Ut-B-2 of the NIH 
Guidelines and Part V of the Points to 
Consider) and will be considered as Minor 
Actions to the NIH Guidelines (see Section 
rV-C-l-b-(2)-{a)). Actions that qualify for 
Accelerated Review (see Section III-B-2) will 
be reviewed and approved by NTH (ORDA) in 
consultation with the RAC Chair and/or one 
or more RAC members, as necessary." 
(Addition) "Certain experiments involving 
the transfer of recombinant DNA into one or 
more human subjects (see Footnote 21) may 
be considered exempt from RAC and/or NIH 
(ORDA) review and/or NIH Director approval 
and only require registration with NIH 
(ORDA) (see Section HI-C-6)." 
(No Changes — Section 1-B through II. 1 
"Section III. Experiments Covered by the NIH 
Guidelines’* 
(Amended] “• • • Any change in 
containment level, which is different from 
those specified in the NIH Guidelines may 
not be initiated without the express approval 
of NIH (ORDA) (see Minor Actions, Section 
rV-G-l-b-(2) and its subsections.)" 
“Section lU-A Experiments that Require 
RAC Review and NIH and IBC Approval 
Before Initiation” 
(Amended) “Experiments in this category 
are considered Major Actions to the NIH 
Guidelines (see Section IV-0-l-b-{l)) and 
cannot be initiated without submission of 
relevant information on the proposed 
exp>erimcnt to NIH, the publication of the 
proposal in the Federal Register for 15 days 
of comment, review by the RAC, and specific 
approval by NIH (not applicable for 
Expiedited Review single patient human gene 
transfer experiments considered under Part 
VI of the Points to Consider), The 
containment conditions for such experiments 
will be recommended by the RAC and set by 
NIH at the time of approval. Such 
experiments also require IBC approval before 
initiation. Specific experiments already 
approved in this section may be obtained 
firora ORDA, NIH, Building 31, room 4B11, 
Bethesda, Maryland 20892.” 
(No Chaiiges — Section IR-A-1 through IR- 
A-2). 
(AmeUdedl “Section IU-A-3. Certain 
experiments involving the deliberate transfer 
of recombinant DNA or DNA or RNA derived 
from recombinant DNA into one or more 
human subjects (see Footnote 21) shall be 
considered Major Actions (see Section IV-C— 
l-b-(l)-(d)), and shall require RAC review 
and NIH Director approval, if determined by 
NIH (ORDA). in consultation with the RAC 
Chair and one or more RAC members, as 
necessary, to: (i) Represent novel 
characteristics (e.g., target disease or vector), 
(ii) represent an uncertain d^ree to risk to 
human health or the environment, or (iii) 
contain information determined to require 
further public review. The requirement for 
RAC review should not be considered to 
preempt any other required review of 
experiments with one or more human 
subjects. Relevant IBC and Institutional 
Review Board (IRB) reviews of the proposal 
should be completed before submission to 
NIH. See Part III-A of the Points to Consider 
for guidelines for submission of human gene 
transfer protocols. Certain experiments 
involving the deliberate tranter of 
recombinant DNA or DNA or RNA derived 
from recombinant DNA into one or more 
human subjects may qualify for the 
Accelerated Review process (see Section III- 
B-2). Certain categories of experiments 
involving the deliberate transfer of 
recombinant DNA or DNA or RNA derived 
from recombinant DNA into one or more 
human subjects and that are not covered by 
Footnote 21. may be considered exempt from 
RAC and/or NIH (ORDA) review and/or NIH 
Director approval and only require 
registration with NIH (ORDA) (see Section 
Ul-C-6)." 
(No Changes — Section Ill-B throu^ III-B- 
l(l).l 
(Additionl "Section IlI-B-2. Human Gene 
Transfer Experiments that Quality for 
Accelerated Review and Approval by NIH 
(ORDA)" 
(Addition) "As determined by the NIH 
(ORDA). in consultation with the RAC Chair 
and one or more RAC members, as necessary, 
certain categenies of human gene transfer 
experiments may be conside^ as Minor 
Actions to the NIH Guidelines and qualify for 
accelerated review and approval (see Section 
rV-C-l-b-(2)(a)). The RAC Chair will 
present a report of all NIH (ORDA)-approved 
human gene transfer protocols at the next 
regularly scheduled RAC meeting. If NTH 
(ORDA) determines that an exjjeriment does 
not qualify for the accelerated review 
[ 4 ] 
Recombinant DNA Research, Volume 19 
