[Federal Register Volume 66, Number 4 (Friday, January 5, 2001)]
[Notices]
[Pages 1146-1147]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-337]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Office of Biotechnology Activities; Recombinant DNA Research: 
Action Under the Guidelines

AGENCY: National Institutes of Health (NIH), PHS, DHHS.

ACTION: Notice of Action Under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules (NIH Guidelines).

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SUMMARY: This notice amends the NIH Guidelines to set forth NIH's 
policy on in utero gene transfer clinical research. At the present 
time, there is insufficient basic and preclinical data to justify the 
conduct of in utero gene transfer clinical research. Before any in 
utero gene transfer clinical trial could proceed, significant 
additional preclinical and relevant clinical studies addressing 
biodistribution, toxicity, and efficiency of vector transduction would 
be required, as would further deliberations of the ethical issues 
associated with this research. As new knowledge evolves from basic, 
preclinical, and relevant clinical research and as the ethical issues 
are addressed, the NIH would consider in utero gene transfer clinical 
protocols for review by the Recombinant DNA Advisory Committee (RAC).

FOR FURTHER INFORMATION CONTACT: Background documentation and 
additional information can be obtained from the Office of Biotechnology 
Activities (OBA), National Institutes of Health, MSC 7010, 6000 
Executive Boulevard, Suite 302, Bethesda, Maryland 20892-7010, Phone 
301-496-9838, FAX 301-496-9839. The OBA Web site is located at http://www.nih.gov/od/oba/.

Background Information

    In September 1998, the NIH RAC discussed two preliminary proposals 
for human in utero gene transfer and

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recommended a comprehensive public review of the scientific and ethical 
issues raised by such studies. In response, NIH convened a national 
Gene Therapy Policy Conference on Prenatal Gene Transfer: Scientific, 
Medical, and Ethical Issues (January 7-8, 1999) to further explore 
these issues.
    The findings and conclusions of the Conference indicated that, at 
present, there is insufficient preclinical data to support the 
initiation of clinical trials involving in utero gene transfer clinical 
research. A substantial number of critical scientific, safety, ethical, 
legal, and social issues must be addressed before clinical trials 
proceed in this arena including: (1) Efficiency of gene transfer to 
target cells; (2) specificity of delivery to target cells; (3) level, 
duration, and regulation of gene expression; (4) appropriate disease 
candidates; (5) fetal immune response to transgene products and/or 
vectors; (6) emergence of fetal immune tolerance; (7) effects of gene 
transfer on pre- and post-natal development; (8) possibility of 
generation and activation of transmissible vector or virus; (9) 
possibility of initiating oncogenic or degenerative processes; (10) 
limitations related to the accuracy of disease diagnosis; (11) 
implications of diagnostic limitations on the design and conduct of 
clinical trials; (12) elements of optimal clinical trial design and 
analysis; (13) potential risk to the fetus and acceptable level of risk 
to the fetus in human experimentation; (14) potential risk to the 
pregnant woman; (15) detection and assessment of inadvertent germ-line 
transmission; (16) ethical issues specific to the fetus; (17) ethical 
issues specific to the pregnant woman; (18) patient recruitment/
enrollment processes; (19) informed consent issues; (20) societal 
issues; and (21) legal issues. (See http://www4.od.nih.gov/oba/gtpcreport.pdf for further information.)
    In March 1999, RAC discussed the findings and conclusions of the 
conference and developed the following consensus statement: ``The RAC 
continues to explore the issues raised by the potential of in utero 
gene transfer research. However, at present, the members unanimously 
agree that it is premature to undertake any human in utero gene 
transfer experiment.'' After providing an opportunity for public 
comments (64 FR 43884), the RAC unanimously recommended that this 
consensus statement be adopted as policy and incorporated into the NIH 
Guidelines (Appendix M). The NIH is implementing this recommendation 
through this notice of action.

Action Amending the NIH Guidelines

Appendix M. Points to Consider in the Design and Submission of 
Protocols for the Transfer of Recombinant DNA Molecules into One or 
More Human Research Participants (Points to Consider)

    Appendix M is amended by adding the following paragraph after the 
third paragraph:
    ``The RAC continues to explore the issues raised by the potential 
of in utero gene transfer clinical research. However, the RAC concludes 
that, at present, it is premature to undertake any in utero gene 
transfer clinical trial. Significant additional preclinical and 
clinical studies addressing vector transduction efficacy, 
biodistribution, and toxicity are required before a human in utero gene 
transfer protocol can proceed. In addition, a more thorough 
understanding of the development of human organ systems, such as the 
immune and nervous systems, is needed to better define the potential 
efficacy and risks of human in utero gene transfer. Prerequisites for 
considering any specific human in utero gene transfer procedure include 
an understanding of the pathophysiology of the candidate disease and a 
demonstrable advantage to the in utero approach. Once the above 
criteria are met, the RAC would be willing to consider well 
rationalized human in utero gene transfer clinical trials.''
    OMB's ``Mandatory Information Requirements for Federal Assistance 
Program Announcements'' (45 FR 39592) 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 virtually every 
NIH and Federal research program in which recombinant DNA techniques 
could be used, it has been determined not to be cost effective or in 
the public interest to attempt to list these programs. 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: December 28, 2000.
Ruth L. Kirschstein,
Acting Director, National Institutes of Health.
[FR Doc. 01-337 Filed 1-4-01; 8:45 am]
BILLING CODE 4140-01-P