[Federal Register: October 20, 2005 (Volume 70, Number 202)]
[Rules and Regulations]               
[Page 61047-61049]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20oc05-13]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

42 CFR Part 73

 
Possession, Use, and Transfer of Select Agents and Toxins--
Reconstructed Replication Competent Forms of the 1918 Pandemic 
Influenza Virus Containing Any Portion of the Coding Regions of All 
Eight Gene Segments

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Interim final rule.

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SUMMARY: We are adding reconstructed replication competent forms of the 
1918 pandemic influenza virus containing any portion of the coding 
regions of all eight gene segments to the list of HHS select agents and 
toxins. We are taking this action for several reasons. First the 
pandemic influenza virus of 1918-19 killed up to 50 million people 
worldwide, including an estimated 675,000 deaths in the United States. 
Also, the complete coding sequence for the 1918 pandemic influenza A 
H1N1 virus was recently identified, which will make it possible for 
those with knowledge of reverse genetics to reconstruct this virus. In 
addition, the first published study on a reconstructed 1918 pandemic 
influenza virus demonstrated the high virulence of this virus in cell 
culture, embryonated eggs, and in mice relative to other human 
influenza viruses. Therefore, we have determined that the reconstructed 
replication competent forms of the 1918 pandemic influenza virus 
containing any portion of the coding regions of all eight gene segments 
have the potential to pose a severe threat to public health and safety.

DATES: The interim final rule is effective on October 20, 2005. Written 
comments must be submitted on or before December 19, 2005.

ADDRESSES: Comments on the change to the list of HHS select agents and 
toxins should be marked ``Comments on the reconstructed replication 
competent forms of the 1918 pandemic influenza virus containing any 
portion of the coding regions of all eight gene segments'' and mailed 
to: Centers for Disease Control and Prevention, Division of Select 
Agents and Toxins, 1600 Clifton Rd., MS E-79, Atlanta, GA 30333. 
Comments may be e-mailed to: SAPcomments@cdc.gov.

FOR FURTHER INFORMATION CONTACT: Mark Hemphill, Chief of Policy, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Rd., MS E-79, Atlanta, GA 30333. Telephone: 
(404) 498-2255.

SUPPLEMENTARY INFORMATION: The complete coding sequence for the 1918 
pandemic influenza A H1N1 virus has been recently identified 
(Taubenberger et al., 2005, Nature, vol. 437, pp. 889-893). Scientists 
from the Centers for Disease Control and Prevention together with 
collaborators at Mount Sinai School of Medicine, NY, Armed Forces 
Institute of Pathology, MD, and Southeast Poultry Research Laboratory, 
U.S. Department of Agriculture, GA, reconstructed the 1918 pandemic 
influenza virus by using reverse genetics to study the properties 
associated with its extraordinary virulence (Tumpey et al., 
Characterization of the Reconstructed 1918 Spanish Influenza Pandemic 
Virus, Science 2005 310: 77-80). With the publication of the complete 
coding sequence, it will be possible for other scientists with 
knowledge of reverse genetics technology to reconstruct the 1918 
pandemic influenza virus at other institutions.
    The pandemic influenza virus of 1918-19 killed up to 50 million 
people worldwide, including an estimated 675,000 deaths in the United 
States. The 1918 pandemic influenza virus' (H1N1) most striking feature 
was the unusually high death rate among healthy adults aged 15 to 34 
years. The question of whether the reconstructed 1918 pandemic 
influenza virus should be regulated as a select agent was considered by 
the Intragovernmental Select Agents and Toxins Technical Advisory 
Committee (ISATTAC). The criteria used by the ISATTAC for reviewing the 
reconstructed 1918 pandemic influenza virus for inclusion on the select 
agent list were: degree of pathogenicity, communicability, ease of 
dissemination, route of exposure, environmental stability, ease of 
production, ability to genetically manipulate or alter, long-term 
health effects, acute morbidity, acute mortality, available treatment, 
status of immunity, vulnerability of special populations, and the 
burden or impact on the health care system. Based on these criteria, 
the ISATTAC determined that the reconstructed 1918 pandemic influenza 
virus could pose an immediate severe threat to public health and safety 
if it is not safely and securely maintained. Further, the ISATTAC noted 
that the biological and molecular properties that enabled the 1918 
pandemic influenza virus to cause such widespread illness and death are 
not completely understood and that it is not known how virulent the 
reconstructed virus would be in the population today. In making its 
determination, the ISATTAC considered both the historical data 
regarding the original 1918 pandemic influenza virus and data from 
current in vitro and in vivo animal studies. The apparent virulence of 
this virus, together with the fact that the level of immunity in the 
general population and the ability of the virus to readily transmit 
among persons are unknown at this time, makes it prudent to immediately 
regulate this virus as a select agent. Although studies with this virus 
can lead to significant public health benefits for understanding 
pandemic influenza, improved diagnostics, and the development of more 
effective countermeasures, there are also potential risks of the misuse 
of this agent for purposes of bioterrorism as well as accidental 
release. Thus, if misused, the 1918 pandemic influenza virus may pose a 
biological threat to public health and/or national security.
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 (the Bioterrorism Act) requires the regulation of 
each biological agent that has the potential to pose a severe threat to 
public health and safety. Congress recognized that a delay in the 
regulation of such biological agents was contrary to the public 
interest by requiring in the Bioterrorism Act that the initial Select 
Agent regulations be promulgated as an interim final rule. Therefore, 
the Secretary has determined that prior notice and opportunity for 
public

[[Page 61048]]

comment are contrary to the public interest and there is good cause 
under 5 U.S.C. 553 for making this rule effective less than 30 days 
after publication in the Federal Register. We will consider comments 
that are received within 60 days of publication of this rule in the 
Federal Register. After the comment period closes, we will publish 
another document in the Federal Register. The document will include a 
discussion of any comments we receive and any amendments that will be 
made to the rule as a result of the comments. In addition to seeking 
comments on the addition of this agent to the HHS list of select agents 
and toxins, we are also seeking comments on the regulation of 
reconstructed viruses that contain less than all eight gene segments 
from the 1918 pandemic influenza virus and if there are certain 
experiments with such constructs or with the fully reconstructed 1918 
pandemic influenza virus that should be added to the ``Restricted 
experiments'' provisions of the regulation.
    An entity must apply to the CDC Division of Select Agents and 
Toxins to possess, use, or transfer reconstructed replication competent 
forms of the 1918 pandemic influenza virus containing any portion of 
the coding regions of all eight gene segments. The CDC Division of 
Select Agents and Toxins will review the entity's biosafety plan to 
ensure that it provides a comprehensive risk assessment of the proposed 
research and adequately ensures appropriate biosafety measures. The CDC 
Division of Select Agents and Toxins will conduct a biosafety review of 
proposed experiments with the reconstructed 1918 pandemic influenza 
virus on a case-by-case basis. The ``Interim CDC-NIH Recommendation for 
Raising the Biosafety Level for Laboratory Work Involving 
Noncontemporary Human Influenza Viruses'' excerpted from the draft CDC/
NIH Biosafety in Microbiological and Biomedical Laboratories, 5th 
edition will be used as the minimum containment for such experiments. 
However, in some cases supplemental biosafety measures may be deemed 
appropriate after review of the proposed experiments.
    The case-by-case review by CDC's Division of Select Agents and 
Toxins will continue until further data are available that may result 
in changes to biosafety guidelines for work with the reconstructed 1918 
pandemic influenza virus. Until such revised guidelines are available, 
entities should refer to the ``Interim CDC-NIH Recommendation for 
Raising the Biosafety Level for Laboratory Work Involving 
Noncontemporary Human Influenza Viruses.'' In accordance with these 
interim guidelines, work with such viruses should proceed with extreme 
caution and the viruses should be handled, at a minimum, under high-
containment (Biosafety Level 3-enhanced) laboratory conditions. 
Enhancements should include the use of powered air purifying 
respirators, change-of-clothing and shower-out requirements, use of 
HEPA filtration for treatment of exhaust air, and a stringent medical 
surveillance and response plan. In addition to these currently 
published interim guidelines, annual vaccination with the currently 
licensed influenza vaccine is strongly recommended and antiviral 
prophylaxis should be available for individuals working with 
reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments.
    The addition of the 1918 pandemic influenza virus to the HHS select 
agents and toxins list is effective immediately. Entities that intend 
to possess, use, or transfer this agent will be required to either 
register in accordance with 42 CFR part 73, or amend their current 
registration in accordance with Sec.  73.7(h).

Paperwork Reduction Act

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), the information collection or 
recordkeeping requirements included in this interim final rule have 
been approved by the Office of Management and Budget (OMB) under OMB 
control number 0920-0576.
    Please send written comments on the new information collection 
contained in this interim final rule to Seleda Perryman, CDC Assistant 
Reports Clearance Officer, 1600 Clifton Road, MS-D74, Atlanta, GA 
30333. Copies of this information collection may be obtained from 
Seleda Perryman, CDC Assistant Reports Clearance Officer, at (404) 639-
4794 or via e-mail to omb@cdc.gov.
    We expect that the entities who will register for possession, use, 
or transfer of reconstructed replication competent forms of the 1918 
pandemic influenza virus containing any portion of the coding regions 
of all eight gene segments will already be registered with the Select 
Agent Program. This interim final rule will require such an entity to 
amend its registration with the Select Agent Program using relevant 
portions of APHIS/CDC Form 1 (Application for Laboratory Registration 
for Possessing, Use, and Transfer of Select Agents and Toxins). 
Estimated time to amend this form is 45 minutes for one select agent. 
Additionally, any registered entity that wishes to transfer 
reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments will be required to submit information using APHIS/
CDC Form 2 (Report of Transfer of Select Agent and Toxins). Estimated 
average time to complete this form is 1 hour, 30 minutes. We estimate 
that only one to five registered entities may add or transfer 
reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments to their registration. Therefore, we calculate that 
there is no increase in the number of respondents, the total number of 
responses may increase by 9, and the total burden hours may increase to 
9 hours and 45 minutes.

Executive Order 12866 and Regulatory Flexibility Act

    This interim final rule has been determined to be significant for 
the purposes of Executive Order 12866 and has been reviewed by the 
Office of Management and Budget.
    This emergency situation makes timely compliance with section 604 
of the Regulatory Flexibility Act (5 U.S.C. 601 et seq.) impracticable. 
We are currently assessing the potential economic effects of this 
action on small entities. Based on that assessment, we will either 
certify that the rule will not have a significant economic impact on a 
substantial number of small entities or publish a final regulatory 
flexibility analysis.

Unfunded Mandates

    The Unfunded Mandates Reform Act at 2 U.S.C. 1532 requires that 
agencies prepare an assessment of anticipated costs and benefits before 
developing any rule that may result in expenditure by State, local, or 
tribal governments, in the aggregate, or by the private sector of $100 
million or more in any given year. This interim final rule is not 
expected to result in any one-year expenditure that would exceed $100 
million.

Executive Order 12988

    This rule has been reviewed under Executive Order 12988, Civil 
Justice Reform. This rule: (1) Would preempt all State and local laws 
and regulations that are inconsistent with this rule; (2) would have no 
retroactive effect; and (3) would not require administrative 
proceedings before parties may file suit in court challenging this 
rule.

[[Page 61049]]

Executive Order 13132

    This rule has been reviewed under Executive Order 13132, 
Federalism. This regulation will not have substantial direct effects on 
the States, on the relationship between the national government and the 
States, or on distribution of power and responsibilities among the 
various levels of government. Therefore, in accordance with Executive 
Order 13132, it is determined that this rule does not have sufficient 
federalism implications to warrant the preparation of a federalism 
summary impact statement.

List of Subjects in 42 CFR Part 73

    Biologics, Incorporation by reference, Packaging and containers, 
Penalties, Reporting and Recordkeeping requirements, Transportation.

    Dated: October 7, 2005.
Michael O. Leavitt,
Secretary.

0
For the reasons stated in the preamble, we are amending 42 CFR part 73 
as follows:

PART 73--SELECT AGENTS AND TOXINS

0
1. The authority citation for part 73 continues to read as follows:

    Authority: 42 U.S.C. 262a; sections 201-204, 221 and 231 of 
Title II of Public Law No. 107-188, 116 Stat. 637 (42 U.S.C. 262a).

0
2. Amend paragraph (b) of Sec.  73.3 by adding the following entry in 
alphabetical order to read as follows:


Sec.  73.3  HHS select agents and toxins.

* * * * *
    (b) * * *
    Reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments.
* * * * *
[FR Doc. 05-20946 Filed 10-17-05; 12:02 pm]

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