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###### Department of Health and Human Services

###### Centers for Disease Control and Prevention 

          - 42 CFR Part 73 

# AGENCY:

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

# ACTION:

Interim final rule. 

# 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                           ( print 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 § 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.                           ( print 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. 

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

# PART 73—SELECT AGENTS AND TOXINS 

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).

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

§ 73.3 

* * * * *

(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] 

BILLING CODE 4160-17-P