[Federal Register Volume 66, Number 238 (Tuesday, December 11, 2001)]
[Notices]
[Pages 64051-64052]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-30513]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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

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

ACTION: Notice of final action under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules (NIH Guidelines).

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SUMMARY: The NIH is amending Appendix B-I of the NIH Guidelines to 
establish criteria for designating strains of E. coli as risk group 1 
agents.

DATES: This final action is effective December 11, 2001.

FOR FURTHER INFORMATION: Background documentation and additional 
information can be obtained from the Office of Biotechnology Activities 
(OBA), 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892-7985, Phone: 
301-496-9838, Fax: 301-496-9839. The OBA web site is located at http://www4.od.nih.gov/oba.

SUPPLEMENTARY INFORMATION: This final action amends Appendix B-I of the 
NIH Guidelines. The proposed action was published for comment in the 
Federal Register on August 13, 2001 (66 FR 42555), and considered by 
the NIH Recombinant DNA Advisory Committee (RAC) at its meeting on 
September 6-7, 2001.

Background Information and Response to Comments

    The background of the August 13, 2001, proposed action was set 
forth fully in the Federal Register notice announcing that action (66 
FR 42555-56). During its September 6-7, 2001, meeting, the RAC 
discussed the proposed action and considered the one public comment 
that was received prior to the meeting. This commenter suggested that 
establishing risk criteria for a specific bacterial strain was 
inappropriate and that the proposed criteria were not general enough 
and too complex. The commenter felt that the current definition of a 
risk group 1 agent should be sufficient. This suggestion was discussed 
by the RAC. It was the RAC's consensus that establishing

[[Page 64052]]

criteria specific for E. coli provided useful guidance in response to 
the specific request from the University of Florida. The RAC 
recommended acceptance of the proposed criteria for designation of E. 
coli as a risk group 1 agent by a vote of 7 in favor, 0 opposed, and 1 
abstention.
    The NIH concurs with the RAC that risk assessment is enhanced by 
the establishment of these criteria for designating strains of E. coli 
as risk group 1 agents. As noted in the proposed action, these criteria 
are not intended to eliminate the need for case-by-case consideration 
of the potential effects of a biological agent on those who may be 
exposed to it (Section II-A-2 of the NIH Guidelines) and are subject to 
reevaluation and change if it is shown that a strain meeting the 
criteria is associated with disease in healthy human adults.
    After the September RAC meeting, an additional comment on the 
proposed criteria was received. This comment, from the American 
Biological Safety Association (ABSA), suggested that the phrase ``rough 
colony morphology'' was not very informative; colony morphology is 
influenced by environmental factors and is not solely dependent upon 
genotype. We concur with that comment; thus, mention of ``rough'' 
colony morphology has been deleted from the criteria. ABSA also 
suggested that the second criterion should be expanded upon to state 
that the bacteria do not carry ``* * *any functional or complete genes 
encoding these factors'' as opposed to ``* * *any genes encoding these 
factors.'' We did not concur with this comment due to the fact that the 
strains of E. coli that have been studied demonstrate the presence or 
entire absence of factor-encoding genes. Strains carrying genes that 
have been rendered non-functional by laboratory manipulations (e.g., 
partial deletions or missense mutations) should not automatically be 
designated as risk group 1 agents.
    Accordingly, the only change in this final action from the proposed 
action is deletion of the reference to ``rough colony morphology.''

Amendments to the NIH Guidelines

    Appendix B-I. Risk Group (RG1) Agents of the NIH Guidelines is 
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); 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. A strain of Escherichia coli (see Appendix 
C-II-A, Escherichia coli K-12 Host Vector Systems, Exceptions) is an 
RG1 agent if it (1) does not possess a complete lipopolysaccharide 
(i.e., lacks the O antigen); and (2) does not carry any active 
virulence factor (e.g., toxins) or colonization factors and does not 
carry any genes encoding these factors.
    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: November 21, 2001.
Ruth L. Kirschstein,
Acting Director, National Institutes of Health.
[FR Doc. 01-30513 Filed 12-10-01; 8:45 am]
BILLING CODE 4140-01-P