Federal Register / Vol. 59, No. 162 / Tuesday, August 23, 1994 / Notices 
43427 
Recurrent or Persistent Head and Neck 
Cancer to the Recombinant DNA 
Advisory Committee for formal review 
and approval. 
IV. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Flotte 
In a letter dated July 14, 1994, Dr. 
Terence R. Flotte of Johns Hopkins 
Children’s Center, Baltimore, Maryland, 
submitted a human gene transfer 
protocol entitled: A Phase I Study of an 
Adeno- associated Virus-CFTR Gene 
vector in Adult CF Patients with Mild 
Lung Disease to the Recombinant DNA 
Advisory Committee for formal review 
and approvaL 
V. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Lyerly 
In a letter received on July 18, 1994, 
Dt. H. Kim Lyerly of Duke University 
Medical Center, Durham, North 
Carolina, submitted a human gene 
transfer protocol entitled: A Pilot Study 
of Autologous H uman Interleukin-2 
Gene Modified Tumor Cells in Patients 
with Refractory or Recurrent Metastatic 
Breast Cancer to the Recombinant DNA 
Advisory Committee for formal review 
and approvaL 
VI. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Whitley 
In a letter dated July 15, 1994, Dr. 
Chester B. Whitley of the University of 
Minnesota, Minneapolis, Minnesota, 
submitted a human gene transfer 
protocol entitled: Retroviral-Mediated 
Transfer of the Iduronate-2-Sulfatase 
Gene Into Lymphocytes for Treatment of 
Mild Hunter Syndrome 
(Mucopolysaccharidosis Type II) to the 
Recombinant DNA Advisory Committee 
for formal review and approval. 
VII. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer ProtocoL/Drs. Holt and Arteaga 
In a letter dated July 15, 1994, Drs. 
Jeffrey Holt and Carlos B. Arteaga of 
Vanderbilt University, Nashville, 
Tennessee, submitted a human gene 
transfer protocol entitled: Gene Therapy 
for the Treatment of Metastatic Breast 
Cancer by In Vivo Infection with Breast- 
Targeted Retroviral Vectors Expressing 
Antisense c-fos or Antisense omyc RNA 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. 
VnL Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Transfer ProtocoL/Drs. Eck, Alavi 
In a letter dated July 15, 1994, Drs. 
Stephen L. Eck and Jane B. Alavi of the 
University of Pennsylvania Medical 
Center, Philadelphia, Pennsylvania, 
submitted a human gene transfer 
protocol entitled: Treatment of 
Advanced CNS Malignancy w/the 
Recombinant Adenovirus 
H5.020RSVTK: A Phase I Trial to the 
Recombinant DNA Advisory Committee 
for formal review and approvaL 
IX. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Albelda 
In a letter received on July 18, 1994, 
Dr. Steven M. Albelda of the University 
of Pennsylvania Medical Center, 
Philadelphia, Pennsylvania, submitted a 
human gene transfer protocol entitled: 
Treatment of Advanced Mesothelioma 
with the Recombinant Adenovirus 
H5.010RSVTK: A Phase I Trial to the 
Recombinant DNA Advisory Committee 
for formal review and approvaL 
X. Amendments to Sections I, HI, IV, V, 
and Appendix M of the NIH Guidelines 
Regarding Consolidated Review of 
Human Gene Transfer Protocols 
On July 18-19, 1994, the National 
Task Force on AIDS Drug Development 
held an open meeting for the purpose of 
identifying barriers to AIDS Drug 
Discovery that included a proposal to 
streamline the dual review process for 
human gene transfer experiments. 
Members of the Task Force 
recommended a consolidated review 
process to enhance interactions between 
the NIH and the FDA. As a result of the 
Task Force's deliberations, 
recommendations were adopted in order 
to eliminate any unnecessary overlap 
between the FDA and NIH review of 
human gene transfer proposals. Both 
Drs. Varmus and Kessler noted that their 
respective agencies would cooperate 
fully to effect the changes necessary to 
implement these recommendations. The 
recommendations were: 
“The NIH and FDA recommend that 
the RAC become advisory to both the 
NIH Director and the FDA with regard 
to the review of human gene transfer 
protocols. In the interest of maximizing 
the resources of both agencies and in 
simplifying the method and period for 
review of research protocols involving 
human gene transfer, it is planned that 
the FDA and NIH institute a new 
consolidated review process that 
incorporates the following principal 
elements: 
(1) All gene transfer protocols shall be 
submitted directly to the FDA. 
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. 
(2) Upon receipt, FDA review will 
proceed. The NIH Office of 
Recombinant DNA Activities (ORDA) 
staff will simultaneously evaluate the 
protocol for possible RAC review. 
(3) Factors which may contribute to 
the need for RAC review include: (1) 
novel approaches, (2) new diseases, (3) 
unique applications of gene transfer, 
and (4) other issues that require further 
public review. 
(4) 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 reviewers 8 weeks 
prior to the next quarterly RAC 
meeting.) 
(5) Semi-annual data reporting 
procedures will reiqgin the 
responsibility of NIH (ORDA). Semi- 
annual data reports will be reviewed by 
the RAC in a public forum.” 
Investigators will no longer be 
required to provide a separate 
submission to NTR/ORDA for RAC 
review. The FDA Division of Cellular 
and Gene Therapies will forward a copy 
of each submission to NIH/ORDA. Any 
protocol submitted < 8 weeks before a 
RAC meeting will be reviewed at the 
following quarterly RAC meeting. 
The RAC will make recommendations 
regarding approval/disapproval of 
protocols, including any relevant 
stipulations, to the NIH Director. The 
NIH Director will transmit the RACs 
recommendations/stipulations to the 
FDA Commissioner. 
The FDA will consider such 
recommendations/stipulations and will 
be responsible for completion of review. 
The RAC and NIH/ORDA will no longer 
have the responsibility for reviewing 
material submitted in response to 
stipulation requirements or for the 
review of minor modifications to human 
gene transfer protocols. 
The following proposed amendments 
to the NIH Guidelines reflect the new 
streamlined review process. 
Section I (Scope of the NIH Guidelines) 
currently reads: 
"Section I. Scope of the NIH 
Guidelines 
"Section I-A. Purpose 
"The purpose of tne NIH Guidelines 
is to specify practices for constructing 
and handling: (i) recombinant 
deoxyribonucleic add (DNA) molecules, 
and (ii) organisms and viruses 
containing recombinant DNA 
molecules. 
Recombinant DNA Research, Volume 20 
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