SUPPLEMENTARY INFORMATION:

The Preamble to this notice of proposed rulemaking is organized as follows:

I. Public Participation

II. Background

III. Changes to 42 CFR Part 73, Modifications to the List of Select Agents and Toxins Being Considered

A. Coxiella burnetii

B. Rickettsia prowazekii

C. Bacillus anthracis Pasteur strain

D. Brucella abortus, B. melitensis, and B. suis

IV. References

I. Public Participation

Interested persons or organizations are invited to participate in this rulemaking by submitting written views, recommendations, and data. Comments are invited on any topic related to this rulemaking.

In addition, HHS/CDC invites comments specifically as to whether there are biological agents or toxins that should be added or removed from the HHS list of select agents and toxins based on the following criteria, or any other appropriate criteria:

(1) The effect on human health of exposure to the agent or toxin;

(2) The degree of contagiousness of the agent or toxin and the methods by which the agent or toxin is transferred to humans; and

(3) The availability and effectiveness of pharmacotherapies and immunizations to treat and prevent any illness resulting from infection by the agent or exposure to the toxin.

(4) The needs of children and other vulnerable populations.

Comments received, including attachments and other supporting materials, are part of the public record and subject to public disclosure. Do not include any information in your comment or supporting materials that you consider confidential or inappropriate for public disclosure. HHS/CDC will carefully consider all comments submitted in preparation of a proposed final rule.

II. Background

The Bioterrorism Response Act requires the HHS Secretary to establish by regulation a list of biological agents and toxins that have the potential to pose a severe threat to public health and safety. In determining whether to include an agent or toxin on the list, the HHS Secretary considers criteria such as the effect on human health of exposure to an agent or toxin; the degree of contagiousness of the agent and the methods by which the agent or toxin is transferred to humans; the availability and effectiveness of pharmacotherapies and immunizations to treat and prevent illnesses resulting from an agent or toxin; and the needs of children and other vulnerable populations. The current list of HHS select agents and toxins can be found at 42 CFR 73.3 (HHS select agents and toxins) and 42 CFR 73.4 (Overlap select agents and toxins). The list of HHS and Overlap ( printed page 10657) select agents and toxins is available at: http://www.selectagents.gov/​Select%20Agents%20and%20Toxins%20List.html.

The HHS Secretary last republished the list of HHS select agents and toxins in the Federal Register on October 5, 2012 (77 FR 61084). The list of HHS select agents and toxins is divided into two sections. The select agents and toxins listed in § 73.3 (HHS select agents and toxins) are those regulated only by HHS under the authority of the Bioterrorism Response Act (42 U.S.C. 262a). The select agents and toxins listed in § 73.4 (Overlap select agents and toxins) are those regulated by HHS under the authority of the Bioterrorism Response Act and regulated by the U.S. Department of Agriculture under the authority of the Agricultural Bioterrorism Protection Act of 2002(7 U.S.C. 8401).

The Bioterrorism Response Act requires the HHS Secretary to review and republish the list of select agents and toxins on at least a biennial basis. Using government subject matter experts, HHS/CDC conducts the biennial review process in consultation with the HHS/CDC Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC). The ISATTAC recommends changes to the list of HHS select agents and toxins. The ISATTAC is comprised of Federal government employees from CDC, Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response, the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the Department of Homeland Security (DHS), the Department of Defense (DOD), the USDA/Animal and Plant Health Inspection Service (APHIS), USDA/Agricultural Research Service (ARS), and USDA/CVB (Center for Veterinary Biologics). Based on the criteria outlined in the Bioterrorism Response Act, the ISATTAC used the following measures in its review: the degree of pathogenicity (ability of an organism to cause disease), communicability (ability to spread from infected to susceptible hosts), ease of dissemination, route of exposure, environmental stability, ease of production, ability to genetically manipulate or alter, long-term health effects, acute morbidity (illness), acute mortality (death), available treatment, status of host immunity, vulnerability of special populations, and the burden or impact on the health care system.

III. Proposed Changes to 42 CFR Part 73, Modifications to the List of Select Agents and Toxins Being Considered

The purpose of this advanced notice of proposed rulemaking is to seek public comment on the appropriateness of the current list of HHS and Overlap select agents and toxins. Specifically, we are providing an opportunity for interested persons to submit comments, research data, and other information that will better inform us as to whether: (1) There are any other biological agents or toxins that should be added to the list because they have the potential to pose a severe threat to public health and safety; (2) there are any other biological agents or toxins currently on the list that should be removed because they no longer have the potential to pose a severe threat to public health and safety, and/or (3) the biological agents specifically listed in the following paragraphs should be removed or remain on the list.

HHS/CDC is also seeking comments on the following considerations regarding the list of HHS and Overlap select agents:

A. Coxiella burnetii

Coxiella burnetii causes a disease called Q fever. Q fever is an acute febrile rickettsial disease that varies in severity and duration. Should Coxiella burnetii be removed or retained as a HHS select agent? Are there other reasons or research data to support the removal besides the following reasons?

• It is not easily transmitted from person to person (1);
• It has a low mortality rate with antibiotic treatment (2); and
• There is an investigational new drug (IND) vaccine available for at-risk personnel (3).

B. Rickettsia prowazekii

Rickettsia prowazekii causes epidemic typhus. Epidemic typhus is a potentially lethal, louse-borne, disease caused by R. prowazekii. Should Rickettsia prowazekii be removed or retained as a HHS select agent? Are there other reasons or research data to support the removal besides the following reasons?

• It is readily treatable with antibiotics (4);
• The risk of mass casualties is low becauseR. prowazekii can be treated with a single dose of doxycycline when symptoms are present (4); and
• Transmissibility from person to person is low due to the fact thatR. prowazekii is usually transmitted via blood, although it can be spread through inhalation of louse feces.

C. Bacillus anthracis Pasteur Strain

Bacillus anthracis is the bacterium that causes anthrax, an acute disease in animals and humans. However, different strains of B. anthracis have different abilities to cause disease. The Pasteur strain, for example, is unable to produce toxic factors and is not considered harmful to humans. Should B. anthracis Pasteur strain be removed or retained as an Overlap select agent? Are there other reasons or research data to support the removal besides the following reasons?

• B. anthracis Pasteur strain lacks the plasmid that encodes the toxin genes causing disease (6);
• B. anthracis Sterne strain, which lacks the plasmid that encodes for the capsule, was excluded from the requirements of the regulations effective on February 27, 2003 (7-8); and
• Historically, theB. anthracis Pasteur strain has been retained as a select agent to allow for continued oversight of laboratories in which the accidental (or intentional) combination of this strain with the Sterne strain could occur to produce de novo the wild type phenotype B. anthracis. However, a recent study indicates that bacterial transformation of B. subtilis with plasmid DNA ( e.g. pXO1 into Bacillus anthracis Pasteur strain) is inefficient; indicating that transformation with bacteria such as B. anthracis would also be inefficient (9).

D. Brucella abortus, B. melitensis, and B. suis

Brucella abortus, B. melitensis, and B. suis bacteria cause brucellosis, a disease that can spread from animals to humans. Should B. abortus, B. melitensis, and B. suis be removed or retained as select agents? Are there other reasons or research data to support the removal besides the following reasons?

• B. abortus has a low human mortality rate (10);
• B. abortus, B. melitensis, and B. suis are readily treatable with antibiotics (10); and
• Human-to-human transmission is extremely rare, and wildlife carriers in the United States often come into contact with humans without significant transmission (10).

IV. References

1. T.J. Marrie. Q fever. In: Marrie TJ, editor. Q fever. Vol. 1. Boca Raton, FL: CRC Press; 1990. (The disease).

2. M. Maurin and D. Raoult. Q fever. Clin Microbiol Rev. Oct. 1999;12(4):518-53.

3. Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition, http://www.cdc.gov/​biosafety/​ ( printed page 10658) publications/​bmbl5/​BMBL5_​sect_​VIII_​d.pdf.

4. D. Raoult, J.B. Ndihokubwayo, H. Tissot-Dupont, V. Roux, B. Faugere, R. Abegbinni, and R.J. Birtles. Outbreak of epidemic typhus associated with trench fever in Burundi. The Lancet. Aug. 1998; 352 (3125):353-358.

5. D. Raoult, T. Woodward, and J.S. Dumler. The history of epidemic typhus. Infect Dis Clin N Am. Mar. 2004; 18(1):127-140.

6. B.E. Ivins, J.W. Ezzell, J. Jemski, K.W. Hedlund, J.D. Ristroph, and S.H. Leppla. Immunization Studies with Attenuated Strains of Bacillus anthracis. Infection and Immunity. May 1986; 52(2):454-458.

7. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases “Anthrax Sterne strain (34F2) of Bacillus anthracis,” http://www.cdc.gov/​nczved/​divisions/​dfbmd/​diseases/​anthrax_​sterne/​.

8. Federal Select Agent Program, “Select Agents and Toxins Exclusions,” http://www.selectagents.gov/​SelectAgentsandToxinsExclusions.html.

9. C. Johnston, B. Martin, G. Fichant, P. Polard, and J.P. Claverys. Bacterial transformation: distribution, shared mechanisms and divergent control. Nature Rev. Microbiol. 2014; 12: 181-196.

10. Center for Food Security and Public Health, “Brucellosis Technical fact sheet,” http://www.cfsph.iastate.edu/​Factsheets/​pdfs/​brucellosis.pdf.