[Federal Register Volume 66, Number 156 (Monday, August 13, 2001)]
[Notices]
[Pages 42555-42556]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-20191]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Office of Biotechnology Activities Recombinant DNA Research: 
Proposed Actions Under the NIH Guidelines

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

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

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

DATES: The public is encouraged to submit written comments on the 
proposed change. Comments may be submitted to the NIH Office of 
Biotechnology Activities (OBA) in paper or electronic form. Comments 
received on or before September 12, 2001 will be considered by NIH. All 
comments received in response to this notice will be available for 
public inspection in the NIH OBA office, 6705 Rockledge Drive, Suite 
750, Bethesda, MD 20892-7985, 301-496-9838, weekdays between the hours 
of 8:30 a.m. and 5 p.m.

FOR FURTHER INFORMATION CONTACT: If you have questions, or want 
additional information about these proposed changes, please contact OBA 
by e-mail at [email protected], or telephone at 301-496-9838. Comments can 
be submitted to the same e-mail address, by fax to 301-496-9839, or 
mail to the Office of Biotechnology Activities address set forth above.

SUPPLEMENTARY INFORMATION: The University of Florida has asked OBA to 
set the risk group level for strain B of the common bacterium E. coli, 
which is non-virulent. Strain B is widely used in industry for large-
scale work (greater than 10 liters of culture) due to increased 
stability of cloned sequences in this strain versus E. coli K-12. 
Currently, the only non-virulent strain of E. coli designated as a risk 
group 1 agent (agents not associated with disease in healthy adult 
humans) in the NIH Guidelines is strain K-12. Potentially pathogenic 
strains of E. coli are designated as risk group 2 agents in the NIH 
Guidelines.
    At the March 2001 RAC meeting, a recommendation was made to define 
the criteria for designating strains of E. coli as risk group 1 agents. 
The establishment of general criteria is preferable to narrowly 
addressing a single strain. The suggested criteria were: ``(1) they 
[the E. coli strain] carry deletions in metabolic genes to engender the 
requirement for specialized laboratory media; and (2) they do not pose 
a threat of disease: they do not carry any active virulence markers nor 
do they make any toxins (nor do they carry the genes for these 
toxins).''
    Following the March 2001 meeting, the University of Florida 
Institutional Biosafety Committee responded that the investigator, Dr. 
Luli (Adjunct Professor in Microbiology and Cell Science at the 
University of Florida and also Research Director for BC International 
Corp.), who made the initial request had reservations regarding the 
requirement for deletions in metabolic genes. Dr. Luli stated that the 
use of specialized laboratory media would pose a problem for large-
scale, industrial work. Dr. Luli suggested that instead of an absolute 
requirement for specialized laboratory media, that the ``* * * scope of 
the [first] requirement be broadened to simply demonstrate ``crippled'' 
or adversely affected metabolism.'' The rationale for this modification 
is that the strains of E. coli B that Dr. Luli proposes to use have 
reduced growth rates compared to wild type E. coli even in complete, 
rich laboratory media.
    The proposed criteria for designating an E. coli strain as a risk 
group 1 agent were revisited at the June 2001 RAC meeting. Ad hoc 
consultant, Dr. James Kaper, University of Maryland School of Medicine, 
also participated in the RAC review and discussion. During the June 
meeting discussion, it was pointed out that a growth requirement is not 
a current criteria in the NIH Guidelines for designation of E. coli K-
12 as a risk group 1 agent. Accordingly, the criteria for designating 
strains of E. coli as risk group 1 agents were revised as follows: 
``(1) they [the E. coli strain] do not possess a complete 
lipopolysaccharide (i.e., they lack the O antigen and have a ``rough'' 
colony morphology); and (2) they do not carry any active virulence 
factors--such as--toxin, or colonization factors nor do they carry 
genes for these factors.'' A ``rough'' colony morphology is indicative 
of the absence of a

[[Page 42556]]

complete coat that aids in survival in the intestine and environment.
    The proposed use of general criteria for designating strains of E. 
coli as risk group 1 agents is 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 any general criteria will be subject to reevaluation 
and change in light of evidence that a strain meeting those criteria is 
associated with disease in healthy adult humans.

Proposed Amendments to the NIH Guidelines

    For the reasons stated above, it is proposed to amend Appendix B-I, 
Risk Group (RG1) Agents, to state:

Appendix B-I. Risk Group (RG1) Agents

    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 has a ``rough'' colony morphology); 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.

    Dated: August 3, 2001.
Ruth L. Kirschstein,
Acting Director, National Institutes of Health.
[FR Doc. 01-20191 Filed 8-10-01; 8:45 am]
BILLING CODE 4140-01-P