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Federal Register / Vol. 58, No. 175 / Monday, September 13, 1993 / Notices 
Angeles, California and Dr. Dennis A. 
Casciato of the University of California, 
Los Angeles, California, may conduct 
experiments on 15 HTV(+) asymptomatic 
patients. Patients will receive 3 monthly 
intramuscular injections of the 
retrovirus vector (N2EBenv) encoding 
the HIV-1 mB envelope protein. 
Patients will be monitored for acute 
toxicity, CD4 levels, HIV-specific CTL 
responses, and viral burdens." 
I accept this recommendation, and 
Appendix D-LTV of the NIH Guidelines 
will be added accordingly. 
I. Addition of Appendix D-LV to the 
NIH Guidelines 
In a letter dated March 8. 1993, Dr. 
Arthur Bank of Columbia University. 
New York, New York, indicated the 
intention of Drs. Charles Hesdorffer and 
Karen Antman of the Columbia 
University, College of Physicians and 
Surgeons, New York, New York, to 
submit a human gene therapy protocol 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. The title of this protocol is: 
Human Multi-Drug Resistance (MDR) 
Gene Transfer in Patients with 
Advanced Cancer. This request was 
published for comment in the Federal 
Register of May 4, 1993 (58 FR 26676). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of June 7-8, 1993, by a 
vote of 11 in favor, 5 opposed, and 3 
abstentions. Approval of the protocol 
was contingent on the following 
stipulations: (1) submission of data 
demonstrating the transduction 
efficiency of human CD34(+) cells, and 
(2) providing a description of the assays 
that will be performed on the clinical 
grade supernatant. 
On June 15, 1993, Dr. Charles 
Hesdorffer submitted the transduction 
efficiency data and the assay description 
for the clinical grade supernatant. These 
documents were reviewed by the 
primary reviewers of the protocol. It was 
determined that the revised, document 
met the request of the RAC. The 
following section may be added to 
Appendix D: 
“Appendix D-LV 
“Drs. Charles Hesdorffer and Karen 
Antman of Columbia University College 
of Physicians and Surgeons, New York, 
New York, may conduct experiments on 
20 patients with advanced breast, ovary, 
ana brain cancer. CD34(+)' 
hematopoietic stem cells will be 
isolated from bone marrow, transduced 
with the retrovirus vector, PHaMDRl/A. 
and readministered to patients. Patients 
will be monitored for the presence and 
expression of the MDR-1 gene. The 
investigators will determine whether 
MDR-1 expression increases following 
chemotherapy.” 
I accept this recommendation, and 
Appendix D-LV of the NIH Guidelines 
will be added accordingly. 
/. Addition of Appendix D-LVI to the 
NIH Guidelines 
In a letter dated January 8, 1993, Ms. 
Arvilla L. Trag of Virogenetics 
Corporation, Troy, New York, submitted 
a request on behalf of Dr. Enzo Paoletti 
for reduction in physical containment 
from Biosafety Level 2 to Biosafety 
Level 1 for three poxvirus vectors: 
NYVAC, ALVAC. and TROVAC. This 
request was published for comment in 
the Federal Register of May 4, 1993 (58 
FR 26676). NYVAC is derived from the 
Copenhagen strain of vaccinia virus in 
which 18 viral genes have been deleted. 
ALVAC is derived from an attenuated 
strain of canarypox virus. TROVAC is 
derived from an attenuated strain of 
fowlpox virus. These vectors are 
proposed for use in the production of 
animal vaccines. 
This request was reviewed and 
recommended for approval during the 
RAC meeting of June 7-8, 1993, by a 
vote of 15 in favor, 0 opposed, and 1 
abstention. The following section may 
be added to Appendix D. 
“Appendix D-LVI 
“Dr. Enzo Paoletti of Virogenetics 
Corporation, Troy, New York, may 
conduct experiments with poxvirus 
vectors NYVAC, ALVAC, and TROVAC 
at Biosafety Level 1.” 
I accept this recommendation, and 
Appendix D-LVI of the NIH Guidelines 
will be added accordingly. 
K. Amendment to Section IV-C-3-c of 
the NIH Guidelines Regarding the 
Responsibility of the Office of 
Recombinant DNA Activities 
In a letter dated April 5, 1993, Ms. 
Debra Wilson of the National Institutes 
of Health submitted a request that 
Section TV-C-3-c be amended to delete 
the requirement that the Office of 
Recombinant DNA Activities (ORDA) 
publish the Recombinant DNA 
Technical Bulletin, and to add the 
requirement that ORDA will serve as the 
focal point for data management of the 
NIH-approved human gene transfer 
protocols. 
Section IV-C-3-c currently reads that 
the Office of Recombinant DNA 
Activities shall be responsible for the 
following: 
“IV-C-3-c. Publishing the 
Recombinant DNA Technical Bulletin 
• • t ** 
Section IV-C-3-c proposed wording 
reads that the Office of Recombinant 
DNA Activities shall be responsible for 
the following: 
‘TV-C-3-c. Serve as the focal point 
for data management of NIH-approved 
human gene transfer protocols as 
required in the Reporting Requirements 
section of the Points to Consider." 
This request was published for 
comment in the Federal Register of May 
4. 1993 (58 FR 26676). 
The request was reviewed and 
recommended for approval during the 
RAC meeting of June 7-8, 1993, by a 
vote of 16 in favor, 0 opposed, and 2 
absentions. Section IV-C-3 may be 
amended to read. that the Office of 
Recombinant DNA Activities shall be 
responsible for the following: 
“IV-C-3-c. Serve as the focal point 
for data management of NIH-approved 
human gene transfer protocols as 
required in the Reporting Requirements 
section of the Points to Consider." 
I accept this recommendation, and 
Section IV-C-3-c of the NIH Guidelines 
will be amended accordingly. 
x 
JL Amendment to Section UI-A-4 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 
During the March 1-2, 1993, 
Recombinant DNA Advisory Committee 
meeting, Dr. Robertson Parkman 
requested that the terms subject and 
subjects be amended to read subject(s). 
Section IH-A-4 currently reads: 
“UI-A-4. Deliberate transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into 
human subjects [21] * * 
Throughout the Points to Consider 
document the terms subject and subjects 
are used. This amendment will clarify 
Section m-A-4 and Points to Consider. 
This request was published for 
comment in the Federal Register of May 
4. 1993 (58 FR 26676). 
During the June 7-8, 1993, meeting, 
the committee reviewed the request. 
The committee recommended changing 
the term “subject(s)" to “one or more 
human subjects.” The recommendation 
was approved by a vote of 20 in favor, 
0 opposed, and no abstentions. Section 
III-A— 4 may be amended to read: 
“ffl-A-4. Deliberate transfer of 
recombinant DNA or DNA or RNA 
derived from recombinant DNA into one 
or more human subject [21] * * 
The term “subject” and “subjects” 
will be changed throughout the NIH 
Guidelines to “one or more human 
subjects.” 
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Recombinant DNA Research, Volume 18 
