[Federal Register Volume 72, Number 210 (Wednesday, October 31, 2007)]
[Notices]
[Pages 61661-61662]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-21404]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Office of Biotechnology Activities; Recombinant DNA Research: 
Action Under the NIH Guidelines for Research Involving Recombinant DNA 
Molecules (NIH Guidelines)

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

ACTION: Notice of final action under the NIH Guidelines.

-----------------------------------------------------------------------

SUMMARY: Specific proposals to conduct research involving the 
deliberate transfer of a drug resistance trait to a microorganism that 
causes disease in humans have been reviewed by the Recombinant DNA 
Advisory Committee (RAC) and approved by the NIH Director. Approval of 
these experiments constitutes a Major Action under section III-A-1 of 
the NIH Guidelines.

DATES: This final action is effective September 24, 2007.

FOR FURTHER INFORMATION: Background documentation and additional 
information can be obtained from the Office of Biotechnology Activities 
(OBA), National Institutes of Health, 6705 Rockledge Drive, Suite 750, 
MSC 7958, Bethesda, Maryland 20892-7958; e-mail at [email protected], or 
telephone at 301-496-9838. The NIH/OBA Web site is located at: http://www4.od.nih.gov/oba/.

SUPPLEMENTARY INFORMATION: This final action allows Dr. Dan Rockey and 
Dr. Walter Stamm (at Oregon State University and the University of 
Washington, respectively) to deliberately transfer a gene encoding 
tetracycline resistance from Chlamydia suis (a swine pathogen) into C. 
trachomatis (a human pathogen). This approval is specific to Drs. 
Rockey and Stamm and research with these resistant organisms may only 
occur under the conditions outlined below. It should be

[[Page 61662]]

noted that any work involving the introduction of tetracycline 
resistance into Chlamydia by other investigators would need to be 
reviewed by the RAC and specifically approved by the NIH Director.

Background Information and Response to Comments

    On May 9, 2007, background on the proposed action, and information 
on how to submit public comment, was published in the Federal Register 
(72 FR 26415). On June 20, 2007, the RAC discussed the proposed action 
at its quarterly public meeting and reviewed the one public comment 
received. The RAC recommended to the NIH Director that this work be 
allowed to proceed under Biosafety level (BL) 2+ containment with 
additional provisions/stipulations. On September 24, 2007, the NIH 
Director approved the proposed experiments with the following 
conditions.
    (1) Tetracycline resistance will only be introduced into non-ocular 
strains of C. trachomatis. In conducting this work on tetracycline 
resistance in C. trachomatis, the following containment standard must 
be followed:
    (2) All research involving the introduction of tetracycline 
resistance into C. trachomatis must be performed at BL 2 using BL3 
practices (referred to as BL2+). The NIH Guidelines articulates 
requirements for BL2 laboratory facilities and equipment in Appendices 
G-II-B-3 and G-II-B-4 while BL3 practices are described in Appendices 
G-II-C-1 and C-2 of the NIH Guidelines. Specifically, the following BL3 
practices must be followed:
    (a) Access must be restricted to well-trained personnel whose 
presence is required for the conduct of this work, and
    (b) The investigators must use sealed centrifuge rotors and tubes.
    (3) In addition, the following procedures and practices must be 
followed:
    (a) Cup sonication must be used rather than probe sonication to 
separate the infectious form [elementary bodies (EB)] from the 
metabolically active [reticulate bodies (RB)] form of the bacterium.
    (b) If possible, consider using other techniques that do not 
involve the potential for the generation of aerosols, such as freeze-
thaw, to separate EBs from RBs.
    (c) No work with the Chlamydia serovars A, B, or C, which cause the 
ocular disease trachoma, may be conducted in the same laboratory in 
which tetracycline resistance is being introduced into C. trachomatis 
serovars that cause genital disease (L, E and G).
    (d) An assay to detect the tetracycline resistant genetic element 
should be developed so that, in the event of a laboratory acquired 
infection, it will be possible to determine whether the genetically 
modified strain of Chlamydia is the source of the infection.
    (e) The following preventive health surveillance steps should be 
implemented for any member of the laboratory working with tetracycline 
resistant C. trachomatis:
    (i) In addition to being trained on proper biosafety practices, 
laboratory workers must be provided education on the possible clinical 
manifestations of laboratory acquired chlamydial infection.
    (ii) Each laboratory must have a detailed, written action plan 
outlining the specific steps to be taken in the case of a laboratory 
exposure or infection. This plan should include at a minimum:
    (1) Identification of key personnel who would provide diagnostic 
testing and treatment;
    (2) Instructions on managing exposures or infections discovered 
during off hours (after close of business, holidays, weekends, etc.);
    (3) Specific recommendations for managing azithromycin-allergic or 
sensitive lab workers; and a provision excluding individuals with known 
macrolide antibiotic allergies from working on these experiments;
    (4) Specific recommendations for treatment of infected laboratory 
personnel who develop side effects while being treated with 
azithromycin, and
    (5) Specific precautions to be taken by infected laboratory workers 
with respect to protecting close contacts (e.g. family members) from 
further infection.
    (iii) In order to ensure that laboratory members will receive 
adequate healthcare in the event of infection, an outreach program 
should be developed to inform healthcare providers who may treat 
laboratory members about the diagnosis and treatment of tetracycline-
resistant Chlamydia. In addition, members of the laboratory should be 
provided with a medical card that includes at least the following 
information:
    (1) Identification of the personnel responsible for providing 
diagnosis and treatment;
    (2) A CDC telephone number for reporting the infection and 
obtaining treatment recommendations, and
    (3) A twenty-four hour contact number for the principal 
investigators.
    (4) Finally, if tetracycline resistant C. trachomatis is 
transferred to other laboratories, the investigators working with this 
tetracycline resistant Chlamydia must follow the identical practices 
and procedures set forth by the NIH Director. It is the responsibility 
of Dr. Rockey and Dr. Stamm to ensure and document that the 
investigators to whom they transfer these strains are apprised of and 
agree to abide by these requirements. As noted, however, since the NIH 
Director's approval for the de novo creation of tetracycline resistant 
strains of non-ocular serovars of C. trachomatis applies only to 
experiments conducted by Drs. Rockey and Stamm, any work involving the 
introduction of tetracycline resistance into Chlamydia by other 
investigators would need to be reviewed by the RAC and specifically 
approved by the NIH Director.

    Dated: October 23, 2007.
Amy P. Patterson,
Director, Office of Biotechnology Activities, National Institutes of 
Health.
 [FR Doc. E7-21404 Filed 10-30-07; 8:45 am]
BILLING CODE 4140-01-P