Federal Register / Vol. 59, No. 162 / Tuesday, August 23, 1994 / Notices 
43431 
modify stably the genome of cells of one 
or more human subjects (see Sections 
ffl-A-2, m-B-2, and m-B-3)." 
Renumber Section V-W to Section V- 
U. 
Appendix M is revised to read as 
follows: 
"Appendix M. Human Gene Transfer 
Experiments 
“Appendix M-I. Human Gene 
Transfer Experiments — Submission 
Requirements 
"Appendix M— I— A. Human Gene 
Transfer Experiments — Submission to 
the FDA 
"In the interest of maximizing the 
resources of both the NIH and the FDA 
and in simplifying the method and 
period for review, research protocols 
involving the deliberate transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into 
human subjects will be submitted 
directly to the FDA and considered 
through a consolidated review process 
involving both the FDA and the NIH. 
Submission will be in the format 
required by the FDA and the same 
format will be used by the RAC when 
public review is deemed necessary. 
Upon receipt, FDA will transmit all 
human gene transfer protocols to the 
NM/ORDA. FDA and NIH/ORDA will 
simultaneously evaluate the protocol for 
possible RAC review. Protocols shall be 
submitted to the Director of the Division 
of Cellular and Gene Therapies, Office 
of Therapeutics Research and Review, 
Center for Biologies Evaluation and 
Research, Food and Drug 
Administration, 1401 Rodtville Pike, 
HFM-515, Rockville, Maryland 20852- 
1448, (301) 496-4709. 
"Appendix M-I-B. Human Gene 
Transfer Experiments Requiring RAC 
Review and NIH Director Consideration 
"Appendix M-I-B-l . Factors that 
may contribute to the need for RAC 
review include: (i) novel approaches, (ii) 
new diseases, (iii) unique applications 
of gene transfer, and (iv) other issues 
that require further public review. 
Whenever possible, Principal 
Investigators will be notified within 15 
working days following receipt of the 
submission whether RAC review will be 
required (RAC reviewed applications 
will be forwarded to RAC primary 
reviewers 8 weeks prior to the next 
quarterly RAC meeting). 
"Appendix M-I-B-2. Written 
comments submitted by the RAC 
primary reviewers shall be submitted to 
NIH/ORDA£4 weeks before the RAC 
meeting at which the protocol will be 
reviewed. 
"Appendix M-I— B— 3. Written 
responses (including critical data in 
response to the primary reviewers’ 
comments) shall be submitted by the 
Principal Investigator to NIH/ORDA £2 
weeks before the RAC meeting at which 
the protocol will be reviewed. 
"Appendix M-I-B-4. Principal 
Investigators will 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 >2 
weeks prior to the RAC meeting are 
prohibited. 
"Appendix M-T-B-5. The RAC 
primary reviewers’ comments should 
include the following: 
“Appendix M-I-B-5-a. Emphasize 
the issues related to gene marking, gene 
transfer, or gene therapy. 
"Appendix M-I-B- 5-b. Examine the 
scientific rationale, scientific context 
(relative to other proposals reviewed by 
the RAC), whether preliminary in vitro 
or in vivo data were obtained in 
appropriate models and are sufficient, 
and whether questions related to safety, 
efficacy, and sodal/ethical 
considerations have been resolved. 
"Appendix M-I-B- 5-c. RAC primary 
reviews should state whether the 
proposal is: (i) acceptable as written, (ii) 
expected to be acceptable with specific 
revisions or after satisfactory responses 
to specific questions raised on review, 
or (iii) unacceptable in its present form. 
“Appendix M-I-B-6. Following 
public review, the RAC's 
recommendations regarding the 
proposal will be transmitted to the NIH 
Director for consideration. 
“Appendix M-I-B-7. The NIH 
Director’s recommendation regarding 
the proposal will be transmitted to the 
FDA Commissioner. 
"Appendix M-I-C Human Gene 
Transfer Experiments — NIH and FDA 
Reporting Requirements 
"Appendix M-I-C-l. Adverse Event 
Reporting 
"Principal Investigators who have 
received approval from the FDA to 
initiate a human gene transfer protocol 
must report any serious adverse event 
immediately to the local Institutional 
Review Board, the NIH Office for 
Protection from Research Risks, Director 
of the Division of Cellular and Gene 
Therapies/FDA, and NIH/ORDA 
followed by the submission of a written 
report filed with each group. Reports 
submitted to NIH/ORDA shall be sent to 
the Office of Recombinant DNA 
Activities, National Institutes of Health, 
6006 Executive Boulevard, Suite 323, 
Bethesda, Maryland 20892-7052, (301) 
496-9838. 
"Appendix M-I-C-2. Semi-Annual 
Data Reporting 
"Principal Investigators who have 
received approval from the FDA to 
initiate a human gene transfer protocol 
shall be required to comply with semi- 
annual data reporting requirements. 
Semi-annual Data Reporting forms will 
be forwarded by NIH/ORDA to the 
Fhindpal Investigators. Data submitted 
in these reports will be evaluated by 
NIH/ORDA and reviewed by the RAC at 
its next regularly scheduled meeting.” 
OMB’s "Mandatory Information 
Requirements forfe^gral Assistance 
Program Announcements” (45 FR 
39592, June 11, 1980) requires a 
statement concerning the official 
government programs contained in the 
Catalog of Federal Domestic Assistance. 
Normally, NIH lists in its 
announcements the number and title of 
affected individual programs for the 
guidance of the public. Because the 
guidance in this notice covers not only 
virtually every NIH program but also 
essentially every Federal research 
program in which DNA recombinant 
molecule techniques could be used, it 
has been determined not to be cost 
effective or in the public interest to 
attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included as many 
Federal agencies, as well as private 
organizations, both national and 
international, have elected to follow the 
NIH Guidelines. In lieu of the 
individual program listing, NIH invites 
readers to direct questions to the 
information address above about 
whether individual programs listed in 
the Catalog of Federal Domestic 
Assistance are affected. 
Dated: August 10, 1994. 
John K. Uzzell, 
Acting Deputy Director for Science Policy and 
Technology Transfer. 
[FR Doc. 94-20826 Filed 8-22-94; 8:45 am) 
BILUNG CODE 4140-01-P 
Recombinant DNA Research, Volume 20 
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