[Federal Register Volume 64, Number 90 (Tuesday, May 11, 1999)]
[Notices]
[Pages 25361-25362]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11839]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Office of Recombinant DNA 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 sets forth an action to be taken by the Director, 
National Institutes of Health (NIH), under the NIH Guidelines for 
Research Involving Recombinant DNA Molecules (59 FR 34496, amended 59 
FR 40170, 60 FR 20762, 61 FR 1482, 61 FR 10004, 62 FR 4782, 62 FR 
53335, 62 FR 56196, 62 FR 59032, 63 FR 8052, 63 FR 26018).

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

SUPPLEMENTARY INFORMATION: Today's action is being promulgated under 
the NIH Guidelines for Research Involving Recombinant DNA Molecules 
(NIH Guidelines). The proposed action was published for comment in the 
Federal Register on February 17, 1999 (64 FR 7964), and reviewed by the 
NIH Recombinant DNA Advisory Committee (RAC) at its meeting on March 
11, 1999.

I. Amendment to Appendix B-I, Risk Group 1 (RG1) Agents

I-A. Background Information and Decisions on Action Under the NIH 
Guidelines

    On December 11, 1998, ORDA received a facsimile from Dr. Margarita 
C. Curras-Collazo, University of California at Riverside, Riverside, 
California, requesting to lower the containment level (from Biosafety 
Level (BL) 2 to 1) for recombinant adeno-associated virus (AAV) vectors 
produced in the absence of helper viruses. Subsequent to this request, 
ORDA received a telephone call from Ms. Brenda Wong, Biological Safety 
Officer, University of California at San Diego, La Jolla, California, 
asking that this request be reconsidered due to the potential of 
insertional mutagenesis.
    In response to this request, ORDA solicited the opinion of three 
AAV experts and the RAC Chair. All three AAV experts and the RAC Chair 
concurred that the BL1 level of physical containment is appropriate for 
recombinant AAV vectors produced in the absence of helper viruses. The 
rationale for this recommendation was based on the fact that 
experiments involving certain recombinant retroviral vectors, which 
insert randomly into the genome and could potentially cause insertional 
mutagenesis, are designated as BL1 agents.
    Appendix B-I, Risk Group 1 (RG1) Agents, currently reads:
    ``RG1 agents are not associated with disease in healthy adult 
humans. Examples of RG1 agents include asporogenic Bacillus subtilis or 
Bacillus licheniformis (see Appendix C-IV-A, Bacillus subtilis or 
Bacillus licheniformis Host-Vector Systems, Exceptions), Escherichia 
coli-K12 (see Appendix C-II-A, Escherichia coli K-12 Host Vector 
Systems, Exceptions), and

[[Page 25362]]

adeno-associated virus types 1 through 4.
    ``Those agents not listed in Risk Groups (RGs) 2, 3 and 4 are not 
automatically or implicitly classified in RG1; a risk assessment must 
be conducted based on the known and potential properties of the agents 
and their relationship to agents that are listed.''
    Appendix B-1, Risk Group 1 (RGI) Agents, is proposed to read:
    ``RGI agents are not associated with disease in healthy adult 
humans. Examples of RG1 agents include asporogenic Bacillus subtilis or 
Bacillus licheniformis (see Appendix C-IV-A, Bacillus subtilis or 
Bacillus licheniformis Host-Vector Systems, Exceptions), Escherichia 
coli K-12 (see Appendix C-II-A, Escherichia coli K-12 Host Vector 
Systems, Exceptions), adeno-associated virus types 1 through 4, and 
recombinant AAV constructs, in which the transgene does no encode 
either a tumor suppressor or a toxin molecule and are produced in the 
absence of a helper virus.
    ``Those agents not listed in Risk Groups (RGs) 2, 3 and 4 are not 
automatically or implicitly classified in RG1; a risk assessment must 
be conducted based on the known and potential properties of the agents 
and their relationship to agents that are listed.''
    The proposed action was published in the Federal Register on 
February 17, 1999 (64 FR 7964) for public comment.
    On March 11, 1999, the RAC discussed the proposed action to 
Appendix B-I with the opinions of AAV experts and the RAC Chair. A 
motion was made to accept the proposed action that the BL1 physical 
containment is appropriate for recombinant AAV vectors produced in the 
absence of helper viruses with a minor change. In the last sentence of 
the first paragraph delete ``tumor suppressor'' and insert 
``potentially tumorigenic gene product.'' The motion passed by a vote 
of 11 in favor, 0 opposed, and no abstentions.
    The action is detailed in Section I-B--Summary of Action. I accept 
the RAC recommendation, and the NIH Guidelines will be amended 
accordingly.

I-B. Summary of Action

I-B-1. Amendment of Appendix B-1, Risk Group 1 (RG1) Agents

    Appendix B-1 is to be amended to read:
    ``RG1 agents are not associated with disease in healthy adult 
humans. Examples of RG1 agents include asporogenic Bacillus subtilis or 
Bacillus licheniformis (see Appendix C-IV-A, Bacillus subtilis or 
Bacillus licheniformis Host-Vector Systems, Exceptions), Escherichia 
coli K-12 (see Appendix C-II-A, Escherichia coli K-12 Host Vector 
Systems, Exceptions), adeno-associated virus (AAV) types 1 through 4, 
and recombinant AAV constructs, in which the transgene does not encode 
either a potentially tumorigenic gene product or a toxin molecule and 
are produced in the absence of a helper virus.
    ``Those agents not listed in Risk Groups (RGs) 2, 3 and 4 are not 
automatically or implicitly classified in RG1; a risk assessment must 
be conducted based on the known and potential properties of the agents 
and their relationship to agents that are listed.''
    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. 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: April 29, 1999.
Harold Varmus,
Director, National Institutes of Health.
[FR Doc. 99-11839 Filed 5-10-99; 8:45 am]
BILLING CODE 4140-01-M