61206 Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

[Docket No. CDC–2011–0012] 

42 CFR Part 73 

RIN 0920–AA34 

Possession, Use, and Transfer of 

Select Agents and Toxins; Biennial 

Review 

AGENCY: Centers for Disease Control and 

Prevention (CDC), Department of Health 

and Human Services (HHS). 

ACTION: Proposed rule. 

SUMMARY: In accordance with the Public 

Health Security and Bioterrorism 

Preparedness and Response Act of 2002 

(the Bioterrorism Response Act), the 

Centers for Disease Control and 

Prevention (CDC) located within the 

Department of Health and Human 

Services (HHS) has reviewed the list of 

biological agents and toxins that have 

the potential to pose a severe threat to 

public health and safety and is 

proposing to amend and republish the 

list as required by the Bioterrorism 

Response Act. Further, on July 2, 2010, 

the President signed Executive Order 

13546, ‘‘Optimizing the Security of 

Biological Select Agents and Toxins in 

the United States’’ that directed the 

Secretaries of HHS and Agriculture 

(USDA) to designate a subset of the 

select agents and toxins list (Tier 1) that 

presents the greatest risk of deliberate 

misuse with the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure; or public 

confidence; explore options for graded 

protection for these Tier 1 agents and 

toxins to permit tailored risk 

management practices based upon 

relevant contextual factors; and consider 

reducing the overall number of agents 

and toxins on the select agents and 

toxins list. E.O. 13546 also established 

the Federal Experts Security Advisory 

Panel (FESAP) to advise the HHS and 

USDA Secretaries on the designation of 

Tier 1 agents and toxins, reduction in 

the number of agents on the Select 

Agent List, establishment of suitability 

standards for those having access to Tier 

1 select agents and toxins, and 

establishment of physical security and 

information security standards for Tier 

1 select agents and toxins. The tiering of 

the select agents and toxins list will 

allow the application of more optimized 

security measures for those select agents 

or toxins which pose a higher risk to 

public health and safety should they be 

stolen or otherwise misused. 

In addition to addressing the FESAP 

recommendations in this Notice of 

Proposed Rulemaking (NPRM), we are 

also proposing to add two agents, Lujo 

and Chapare viruses to the list; adding 

definitions; and clarifying language 

concerning security, training, biosafety, 

and incident response. These changes 

will increase the usability of the select 

agents and toxins regulations as well as 

providing for enhanced program 

oversight. 

DATES: Comments should be received on 

or before December 2, 2011. 

ADDRESSES: You may submit comments, 

identified by Regulatory Information 

Number (RIN), 0920–AA34 in the 

heading of this document by any of the 

following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Mail: Centers for Disease Control 

and Prevention, Select Agent Program, 

1600 Clifton Road, NE., Mailstop A–46, 

Atlanta, Georgia 30333, Attn: RIN 0920– 

AA34. 

Instructions: All submissions received 

must include the agency name and RIN 

for this rulemaking. All relevant 

comments received will be posted 

without change to http:// 

www.regulations.gov, including any 

personal information provided. 

Docket Access: For access to the 

docket to read background documents 

or comments received or to download 

an electronic version of the NPRM, go 

to http://www.regulations.gov. 

Comments will be available for public 

inspection Monday through Friday, 

except for legal holidays, from 9 a.m. 

until 5 p.m. at 1600 Clifton Road, NE., 

Atlanta, GA 30333. Please call ahead to 

1–866–694–4867 and ask for a 

representative in the Division of Select 

Agents and Toxins to schedule your 

visit. Our general policy for comments 

and other submissions from members of 

the public is to make these submissions 

available for public viewing on the 

Internet as they are received and 

without change. 

FOR FURTHER INFORMATION CONTACT: 

Robbin Weyant, Director, Division of 

Select Agents and Toxins, Centers for 

Disease Control and Prevention, 1600 

Clifton Road, NE., Mailstop A–46, 

Atlanta, Georgia 30333. Telephone: 

(404) 718–2000. 

SUPPLEMENTARY INFORMATION: The 

Preamble to this notice of proposed 

rulemaking is organized as follows: 

I. Background 

II. Proposed Changes to 42 CFR Part 73, 

Including Responses to Comments to the 

ANPRM 

A. Modifications to the List of HHS Select 

Agents and Toxins 

B. Modifications to the List of Overlap 

Select Agents and Toxins 

C. Tiering 

D. Responses to Other Comments and 

Other Proposed Changes 

i. Exclusions 

ii. Security 

iii. Select Agent Inventory 

iv. Definitions 

v. Recombinant/Synthetic Nucleic Acids 

vi. Toxins 

vii. Responsible Official 

viii. Access to Select Agents and Toxins 

ix. Security Plan 

x. Biosafety Plans 

xi. Restricted Experiments 

xii. Incident Response 

xiii. Training 

xiv. Transfers 

xv. Records 

xvi. Administrative Review 

xvii. Guidance Documents 

III. Required Regulatory Analyses 

A. Executive Order 12866 and 13563 

B. Regulatory Flexibility Act 

C. Paperwork Reduction Act 

D. Executive Order 12988: Civil Justice 

Reform 

E. Executive Order 13132: Federalism 

F. Plain Writing Act of 2010 

IV. References 

I. Background 

The Public Health Security and 

Bioterrorism Preparedness and 

Response Act of 2002, Subtitle A 

(Department of Health and Human 

Services) of Title II (Enhancing Controls 

on Dangerous Biological Agents and 

Toxins) of Public Law 107–188 (June 12, 

2002) (42 U.S.C. 262a) (the Bioterrorism 

Response Act), requires the HHS 

Secretary to establish by regulation a list 

of each biological agent and each toxin 

that has 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 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; the potential for 

an agent or toxin to be used as a 

biological weapon; 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 select agents and toxins is 

available at: http:// 

www.selectagents.gov/Select%20

Agents%20and%20Toxins%20

List.html. The Bioterrorism Response 

Act requires that the HHS Secretary 

review and republish the list of select 


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agents and toxins on at least a biennial 

basis. See 42 U.S.C. 262a(a)(2). 

The HHS Secretary last republished 

the HHS select agents and toxins list in 

the Federal Register on October 16, 

2008 (73 FR 61363). The HHS select 

agents and toxins list 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. 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 USDA under 

the authority of the Agricultural 

Bioterrorism Protection Act of 2002 (7 

U.S.C. 8401). 

To fulfill this statutory mandate, the 

Center for Disease Control and 

Prevention’s (CDC) Division of Select 

Agents and Toxins (DSAT) initiated its 

biennial review process, which 

included consultation with CDC’s 

Intragovernmental Select Agents and 

Toxins Technical Advisory Committee 

(ISATTAC) and other subject matter 

experts. The ISATTAC is comprised of 

Federal government employees from the 

CDC, the National Institutes of Health 

(NIH), the Food and Drug 

Administration (FDA), the USDA/ 

Animal and Plant Health Inspection 

Service (APHIS), USDA/Agricultural 

Research Service (ARS), USDA/CVB 

(Center for Veterinary Biologics), the 

Department of Homeland Security 

(DHS), the Department of Defense 

(DOD), and the Biomedical Advanced 

Research and Development Authority 

(BARDA) within the Office of the 

Assistant Secretary for Preparedness 

and Response in HHS. 

CDC also published an ANPRM in the 

Federal Register (75 FR 42363) (July 21, 

2010 ANPRM) inviting comments 

concerning potential changes to part 73 

of Title 42 of the Code of Federal 

Regulations (the select agent 

regulations). We solicited comments 

regarding (1) the appropriateness of the 

current HHS list of select agents and 

toxins; (2) whether there are other 

biological agents or toxins that should 

be added to the HHS list; (3) whether 

biological agents or toxins currently on 

the HHS list should be deleted from the 

list; (4) whether the HHS select agents 

and toxins list should be tiered based on 

the relative bioterrorism risk of each 

biological agent or toxin; and (5) 

whether the security requirements for 

select agents or toxins in the highest tier 

should be further stratified based on 

type of use or other factors. We 

requested recommendations regarding 

the criteria to use to designate high risk 

select agents and toxins and those 

recommendations were included in the 

interagency working group discussions 

on the matter. Relevant issues raised by 

the comments are discussed below in 

‘‘II. Proposed Changes to 42 CFR part 

73.’’ 

On July 2, 2010, President Obama 

signed Executive Order (E.O.) 13546: 

‘‘Optimizing the Security of Biological 

Select Agents and Toxins in the United 

States’’ that directed the Secretaries of 

HHS and USDA to (1) designate a subset 

of the select agents and toxins list (Tier 

1) that presents the greatest risk of 

deliberate misuse with the most 

significant potential for mass casualties 

or devastating effects to the economy, 

critical infrastructure; or public 

confidence; (2) explore options for 

graded protection of Tier 1 agents and 

toxins to permit tailored risk 

management practices based upon 

relevant contextual factors; and (3) 

consider reducing the overall number of 

agents and toxins on the select agents 

and toxins list. E.O. 13546 also 

established the FESAP to advise the 

HHS and USDA Secretaries on the 

designation of Tier 1 agents and toxins, 

reduction in the number of agents on 

the Select Agent List, establishment of 

personnel reliability standards for those 

having access to Tier 1 select agents and 

toxins, and establishment of physical 

security and information security 

standards for Tier 1 select agents and 

toxins. E.O. 13546 is available at: 

http://edocket.access.gpo.gov/2010/pdf/ 

2010-16864.pdf. The FESAP provided 

its recommendations to the HHS and 

USDA Secretaries on November 2, 2010. 

The FESAP recommendations addressed 

the reduction of the list of select agents 

and toxins, the identification of a subset 

of the list that includes those that 

presents the greatest risk of deliberate 

misuse with the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure; or public 

confidence; and the optimization of 

security programs at registered entities. 

In drafting its recommendations to 

modify and stratify the list of select 

agents and toxins, the FESAP utilized 

expert knowledge of the agents, 

combined with information from the 

DHS’s Material Threat Determinations 

of biological agents and toxins. Care was 

used to balance risks identified with the 

Congressional mandate to ensure the 

availability of select agents and toxins 

for research and educational activities. 

Other sources of input that we have 

considered in the drafting of this 

Proposed Rule include the following: 

The National Science Advisory Board 

for Biosecurity, the National Academies, 

and comments received from 

professional societies and the public in 

response to the CDC ANPRM published 

on July 21, 2010. 

The purpose of this notice of 

proposed rulemaking is to seek public 

comment on (1) the appropriateness of 

the current HHS and Overlap list of 

select agents and toxins including 

whether there are other agents or toxins 

that should be added to the HHS or 

Overlap list or whether agents or toxins 

currently on the HHS or Overlap list 

should be deleted from the list; (2) the 

appropriateness of the proposed tiering 

of the select agents and toxins list; (3) 

whether minimum standards for 

personnel reliability, physical and cyber 

security should be prescribed for 

identified Tier 1 agents; and (4) any 

other aspect of the proposed 

amendments to the select agent 

regulations. 

II. Proposed Changes to 42 CFR Part 73 

PROPOSED CHANGES TO 42 CFR PART 73 

Section No. Current Change 

73.0 .................... Applicability and related requirements .... No change. 

73.1 .................... Definitions ................................................ Definitions added: Adjudicated as a mental defective; alien; committed to any 

mental institution; controlled substance; crime punishable by imprisonment for a 

term exceeding 1 year; indictment; information security; lawfully admitted for 

permanent residence; mental institution; occupational exposure; recombinant 

and synthetic nucleic acids; restricted person; unlawful use of any controlled 

substance. 

73.2 .................... Purpose and scope ................................. No change. 

73.3 .................... HHS select agents and toxins ................. Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the HHS list. 


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PROPOSED CHANGES TO 42 CFR PART 73—Continued 

Section No. Current Change 

73.4 .................... Overlap select agents and toxins ............ Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the overlap list. 

73.5 .................... Exemptions for HHS select agents and 

toxins.

Amends the immediate notification list to Tier 1 agents. 

73.6 .................... Exemptions for overlap select agents 

and toxins.

Amends the immediate notification list to Tier 1 agents. 

73.7 .................... Registration and related security risk assessments.No change. 

73.8 .................... Denial, revocation, or suspension of registration.Clarifies language. 

73.9 .................... Responsible Official ................................. Redesignates paragraphs; adds new paragraphs (a)(3), (a)(6). 

73.10 .................. Restricting access to select agents and 

toxins; security risk assessments.

Redesignates paragraphs; adds new paragraph (e); adds clarifying language. 

73.11 .................. Security .................................................... Revises regulatory text—paragraph (b), (c)(2). Redesignates paragraphs; adds 

new paragraphs (c)(8), (c)(9), (c)(10), (e). 

73.12 .................. Biosafety .................................................. Revises paragraphs (a) and (c)(1); replaces ‘‘url’’ in paragraph (c)(3); redesignates paragraph (d); adds new paragraph (d). 

73.13 .................. Restricted experiments ............................ Clarifies language. 

73.14 .................. Incident response .................................... Redesignates paragraphs; adds new paragraphs (d) and (e). 

73.15 .................. Training .................................................... Revises paragraph (a); redesignates paragraphs; adds new paragraph (b). 

73.16 .................. Transfers ................................................. Redesignates paragraphs; adds new paragraphs (f), (h), (l). 

73.17 .................. Records ................................................... Revises paragraph (a)(1); redesignates paragraphs; adds new paragraph (a)(2). 

73.18 .................. Inspections .............................................. No changes. 

73.19 .................. Notification of theft, loss, or release ....... No changes. 

73.20 .................. Administrative review .............................. Revises paragraphs. 

73.21 .................. Civil money penalties .............................. No changes. 

A. Modifications to the List of HHS 

Select Agents and Toxins 

The following changes to the list of 

HHS select agents and toxins are 

proposed based on comments received 

in response to the July 21, 2010 

ANPRM, recommendations from the 

FESAP and ISATTAC, and our review of 

current scientific data regarding select 

agents and toxins. As we discuss below, 

we are proposing to remove 6 select 

agents, add 2 select agents, and identify 

11 select agents and toxins as ‘‘Tier 1’’ 

agents to the HHS list of select agents 

and toxins. 

Proposed Addition of Lujo and Chapare 

Viruses 

On August 19, 2009 (74 FR 41829), we 

proposed the addition of Chapare virus 

to the HHS list of select agents and 

toxins; we did not receive any 

comments regarding that proposal. 

Based on scientific data and risks 

associated with this virus, the ISATTAC 

recommended the addition of Chapare 

virus to the HHS list of select agents and 

toxins. The determination to add 

Chapare virus to the HHS list of select 

agents and toxins was based on the 

following scientific information. The 

HHS list currently includes members of 

the arenaviridae family (Junin, 

Machupo, Sabia, Flexal, Guanarito, and 

Lassa). Arenaviruses are rodent-borne 

viruses, some of which can be 

associated with large hemorrhagic fever 

outbreaks, and untreated case fatalities 

can be in excess of 30 percent. Chapare 

virus is a recently described New World 

arenavirus that is associated with fatal 

hemorrhagic fever syndrome and is 

most closely related to Sabia virus, an 

HHS select agent (Ref 1). Based on the 

ISATTAC recommendation and our 

examination of the current scientific 

data and risks associated with this virus, 

we are proposing to add Chapare to the 

HHS list. 

The ISATTAC also recommended the 

addition of Lujo virus to the HHS list of 

select agents and toxins. Based on this 

recommendation and our examination 

of the current scientific data and risks 

associated with this virus, we are also 

proposing to add Lujo virus. The 

scientific determination was based on 

the fact that the Lujo virus caused a fatal 

outbreak of hemorrhagic fever, has an 

unprecedented high case fatality rate of 

80 percent, has been phylogenetically 

identified as an arenavirus and is 

related to those members of the Old 

World arenaviridae family (Junin, 

Machupo, Sabia, Flexal, Guanarito, and 

Lassa) listed as HHS select agents that 

cause hemorrhagic fever and pose a 

significant risk to public health and 

safety (Ref 2). 

Proposed Removal of Cercopithecine 

Herpesvirus 1 (Herpes B Virus) 

Commenters acknowledged in 

response to the July 21, 2010 ANPRM 

that (1) the Herpes B virus naturally 

infects many species of macaques; and 

(2) can produce a serious, often fatal, 

infection in humans when not treated. 

However, the commenters argued that 

Herpes B virus should not be included 

as a select agent based on the following 

assertions: 

• The inclusion of the virus on the 

list will produce no significant 

improvements in safety for the 

American public. 

• Given the high prevalence of 

infection in non-human primates and 

the relatively few human infections that 

have been recorded, it suggests that the 

virus is not easily transmitted to 

humans. 

• The virus is capable of being treated 

with several available licensed antiviral 

compounds. 

• The virus does not present a 

sufficient risk of infection by the aerosol 

route. 

• The virus is a highly unlikely 

candidate for a bioterrorism agent due to 

its environmental instability and the 

need for direct contact for infection. The 

argument is further enhanced by the 

absence of the virus listed on the NIH’s 

National Institute of Allergy and 

Infectious Diseases lists of Category A, 

B & C Priority Pathogens or the CDC’s 

Category A, B & C Bioterrorism Agents 

lists. 

• The virus is widely available in 

nature. 

The ISATTAC and the FESAP also 

recommended the removal of 

Cercopithecine herpesvirus 1 (Herpes B 

virus) from the HHS list of select agents 

and toxins. We agreed with the 


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commenters, ISATTAC, and FESAP and 

propose to remove Cercopithecine 

herpesvirus 1 (Herpes B virus) from the 

HHS list of select agents and toxins. Our 

rationale for this proposal is based on 

the facts that this virus is not easily 

transmitted to humans, the person-toperson transmission risk is small, the 

numbers of recorded human infections 

are low, and multiple licensed antiviral 

treatments for Herpes B infections are 

available. 

Proposed Removal of Coccidioides 

posadasii/Coccidioides immitis 

Commenters to our July 21, 2010 

ANPRM argued that Coccidioides 

posadasii/Coccidioides immitis should 

not be included as a select agent based 

on the following reasons: 

• The characteristics of Coccidioides 

species do not provide convincing 

properties of an effective agent of 

bioterrorism. 

• The fungi are endemic in the 

southwestern United States, but do not 

cause large epidemics even with high 

prevalence in the air during wind 

storms. 

• Infections caused by the fungi are 

easily treatable by licensed antifungal 

medicines, especially early in disease. 

• The difficulty to use Coccidioides 

species as a bioweapon, and hence the 

need for strict regulation under the 

select agent regulations, is exemplified 

by their non-communicability, lack of 

history of use or development as 

successful biological weapons, and a 

relatively low incidence of symptomatic 

disease following natural infection. 

• Coccidioides species would not be 

an effective bioterrorism weapon 

because the percentage of deaths and 

hospitalizations are low considering the 

number of people infected. 

The FESAP also recommended 

removal of Coccidioides posadasii/ 

Coccidioides immitis from the HHS list 

of select agents and toxins. We agreed 

with the commenters and FESAP and 

propose to remove Coccidioides 

posadasii/Coccidioides immitis from the 

HHS list of select agents and toxins. The 

scientific determination was based on 

the availability of licensed treatments 

for Coccidioides infection and a 

lowering of our assessment of the 

impact of Coccidioides infection on 

human health, as indicated by the high 

proportion of subclinical cases observed 

in endemic areas (Ref 3). 

Proposed Retention of Coxiella burnetii 

Commenters to the July 21, 2010 

ANPRM argued that Coxiella burnetii (Q 

fever) should be removed from the 

select agents and toxins list based on the 

following assertions: 

• Q fever is not contagious and is 

effectively treated with licensed 

antibiotics. 

• It is generally a self-limiting 

infection with potential control by 

licensed vaccination. 

• The ubiquitous nature of Coxiella 

burnetii means that it can be easily 

acquired from environmental sources 

and calls into question the effectiveness 

and procedures for maintaining 

inventories of select agents. 

• Person-to-person transmission of 

the disease is rare and is fatal less than 

one percent of the time. 

• A vaccine is available for this agent 

internationally, but not domestically. 

• The agent is commonly found in 

animal populations within the United 

States. 

However, FESAP and ISATTAC did 

not recommend removing this 

bacterium from the HHS list of select 

agents and toxins. We agreed with the 

FESAP and ISATTAC recommendations 

and propose to retain Coxiella burnetii 

on the HHS select agents and toxins list. 

The determinations to retain this agent 

on the HHS list are its robust 

environmental stability, ease of 

transmission to humans, extremely low 

infectious dose, and prior association of 

this agent with offensive programs. CDC 

invites comments regarding retaining 

this agent on the HHS list of select 

agents and toxins. 

Proposed Removal of South American 

Genotypes of Eastern Equine 

Encephalitis Virus (EEEV) 

Commenters on the July 21, 2010 

ANPRM regarding the proposed 

inclusion of EEEV on the list of select 

agents and toxins argued that EEEV 

should not be included as a select agent 

based on the following reasons: 

• The virus occurs naturally in the 

environment. 

• Direct person-to-person 

transmission does not occur. 

• Local and State health departments 

and mosquito control agencies routinely 

release information regarding the 

location of arboviral activity in the 

community, so upholding strict 

biosecurity measures in a laboratory has 

little or no impact on reducing a 

terrorist’s ability to acquire this agent. 

• Only North American strains of 

EEEV should be regulated because 

transmission patterns limit the 

distribution and epidemic potential of 

South American strains, which are less 

pathogenic. 

We examined the current scientific 

data and noted that strains of EEEV can 

be categorized into two distinct 

genotypes primarily based upon 

geographic distribution: North 

American genotype (NA EEE) and South 

American genotype (SA EEE). The NA 

EEE genotype consists of strains 

obtained from North America and the 

Caribbean while SA EEE genotype 

viruses originate in Central and South 

America. Viruses in the two genotypes 

are distinctly different in their genetics, 

epidemiology, and pathogenicity. NA 

EEE, which are the strains responsible 

for human and equine disease, are all 

genetically very similar to each other 

(less than 3% divergence at the 

nucleotide level) and can be easily 

distinguished from SA EEE genotype 

strains by sequencing. NA EEE genotype 

strains differ from SA EEE viruses by 

greater than 20% at the nucleotide level 

and approximately 10% at the amino 

acid level. Since FESAP agreed with our 

scientific assessment that SA EEE 

genotypes should be removed from the 

HHS list of select agents and toxins, we 

are proposing to remove SA EEE 

genotypes from the HHS list of select 

agents and toxins (Ref 4). 

Proposed Removal of Flexal Virus 

Commenters that responded to the 

July 21, 2010 ANPRM felt that Flexal 

virus should be removed from the HHS 

list of select agents and toxins based on 

the lack of severity of disease and the 

lack of significant outbreaks of disease 

associated with infection with this virus 

in humans. FESAP also recommended 

that Flexal virus be removed from the 

list. Since our research found a lack of 

significant outbreaks of disease 

associated with Flexal virus in humans 

and that this virus would be a highly 

unlikely candidate for a bioterrorism 

agent, we are proposing to remove 

Flexal virus from the HHS list of select 

agents and toxins. 

Proposed Retention of Monkeypox Virus 

Commenters to the July 21, 2010 

ANPRM recommended that Monkeypox 

virus should not be included as a select 

agent based on the following assertions: 

• An effective licensed vaccine is 

available. 

• Promising antivirals are in 

advanced stages of development. 

• The virus is inefficiently 

transmitted from person-to-person. 

We examined the current scientific 

data and noted that there is an increased 

incidence of Monkeypox virus in 

humans as well as studies identifying 

the virus being easily transmitted in 

Gambian rats. A recent study on an 

outbreak in Sudan indicates there is 

much strain variation in level of 

infectivity and severity of disease. 

Concern over the detection of new 

lineages with increased pathogenesis 

has been expressed. Another recent 


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outbreak of Monkeypox virus in the 

United States suggested numerous 

animals could become infected 

complicating the understanding of 

zoonotic maintenance of the virus (Ref 

29–33). 

While there has been documented 

cross protection against Monkeypox 

virus by Vaccinia virus vaccine, the 

decrease in the number of individuals 

with any immunity to the virus is 

drastically declining (since smallpox 

vaccination no longer occurs). Further, 

even though there is a stockpile of 

Vaccinia virus vaccine available, the 

vaccine has numerous undesirable sideeffects that make it less than optimal for 

mass vaccination. There are also several 

antiviral treatments for Monkeypox in 

advanced stages of development, but 

they are not currently available. Thus, 

there is currently no specific treatment 

(Ref 29–33). 

FESAP recommended keeping 

Monkeypox virus on the HHS list of 

select agents and toxins. 

Based on the scientific determination 

outlined above, we are proposing to 

retain Monkeypox virus on the HHS list 

of select agents and toxins. We will 

continue to monitor progress in the 

development of antivirals and other 

means of prevention and control of 

Monkeypox virus infections and invite 

comments on removing a certain clade 

of Monkeypox virus (i.e., West African 

clade of Monkeypox virus) from the 

HHS list of select agents and toxins. 

Proposed Reorganization of Tick-Borne 

Encephalitis Complex Viruses (TBEV) 

Even though we received no 

comments to the July 21, 2010 ANPRM 

regarding the removal of these viruses 

from the HHS list of select agents and 

toxins, we are proposing the removal of 

TBEV Central European subtype from 

the HHS list of select agents and toxins 

for the following scientific reasons: 

• The TBEV Central European Tickborne subtype has been shown to be less 

virulent in humans than the Far Eastern 

subtype (Ref 5). 

• No TBEV vaccines are licensed or 

available in the United States; however 

two safe, effective inactivated TBEV 

vaccines are available internationally. 

FESAP also recommended the 

removal of the TBEV Central European 

subtype from the HHS list of select 

agents and toxins. 

In addition to removing the TBEV 

Central European subtype from the HHS 

list of select agents and toxins, we 

propose to reorganize the listing of the 

TBEV to reflect the current 

nomenclature given by the International 

Committee on Taxonomy of Viruses. For 

TBEV proper, there are now just three 

recognized subtypes: Central European, 

Far Eastern, and Siberian. The Russian 

Spring and Summer encephalitis 

designation is no longer recognized (Ref 

6). Two other viruses on the HHS list of 

select agents and toxins, Kyasanur 

Forest disease virus and Omsk 

Hemorrhagic fever virus, are no longer 

classified as TBEV. In recognition of 

these taxonomic changes, we are 

proposing to include these viruses on 

the HHS list of select agents and toxins 

as follows: 

Tick-borne encephalitis virus 

Far Eastern subtype 

Siberian subtype 

Kyasanur Forest disease virus 

Omsk Hemorrhagic fever virus 

Proposed Retention of Rickettsia 

prowazekii and Rickettsia Rickettsii 

Commenters that responded to the 

July 21, 2010 ANPRM argued that 

Rickettsia prowazekii and Rickettsia 

rickettsii should be removed from the 

HHS list of select agents and toxins 

based on the following assertions: 

• Mimicking transmission by 

arthropod vectors in an effort to 

disperse these pathogens with the intent 

to disrupt society would be challenging 

and technologically unlikely to be 

successful. 

• Common and readily available 

licensed antibiotics are highly effective, 

and contagion is not a threat because 

spread is determined by contact with 

the vectors, not through person-toperson contact. 

• Although Rickettsia prowazekii 

may be a pathogen of military 

significance, Rickettsia rickettsii is not. 

According to the commenter, 

propagation of the pathogens requires 

growth in cultured host cells and 

natural infection occurs by parenteral 

inoculation through a tick vector, so 

mass exposure by aerosolization or 

contamination of food sources is 

unlikely to result in disease. 

• The potential to use this agent as a 

platform to construct a genetically 

engineered new pathogen would be 

extremely difficult. 

• The primary disease associated 

with Rickettsia rickettsii is Rocky 

Mountain Spotted Fever, and the 

symptoms are recognizable and 

marketed diagnostics and treatment are 

readily available. 

• Rickettsia rickettsii should be 

removed because generation of even 

moderate amounts of infectious material 

is exceedingly difficult and requires 

specialized equipment. 

• Rickettsiae are not spread directly 

from person-to-person, would not 

survive if dispersed into the 

environment, and are susceptible to a 

number of readily available licensed 

antibiotics. In addition, there is no 

possibility of eliminating their presence 

in the environment. 

• Potential benefits of lessening 

restriction on research include 

improved diagnostic capabilities and 

better potential for vaccine 

development. 

The FESAP and ISATTAC 

recommended keeping Rickettsia 

prowazekii and Rickettsia rickettsii on 

the HHS list of select agents and toxins. 

Since we agreed with these expert 

panels, we are proposing to retain 

Rickettsia prowazekii and Rickettsia 

rickettsii on the HHS select agents and 

toxins list based on our scientific 

determination regarding the 

environmental stability, low infectious 

dose, aerosol transmission, and clinical 

significance of infection with these 

organisms. 

Proposed Retention of Yersinia pestis 

Commenters that responded to the 

July 21, 2010 ANPRM argued that 

Yersinia pestis should not be included 

as a select agent based on the following 

assertions: 

• Yersinia pestis is naturally 

occurring and does not survive for long 

outside of its rodent host because of 

susceptibility to heat and sunlight. 

• Decontamination of surfaces is 

highly effective in limiting its spread. 

• Licensed treatments are readily 

available for those who may become 

exposed. 

The FESAP and ISATTAC 

recommended that Yersinia pestis 

remain on the HHS list of select agents 

and toxins. 

We agree with the FESAP and 

ISATTAC, and are proposing to keep 

Yersinia pestis on the HHS select agents 

and toxins list based on our scientific 

conclusion regarding the bacterium’s 

high mortality rate, ease of 

dissemination and production, and 

person-to-person transmission of 

Yersinia pestis infections. 

Proposed Reorganization of 

Staphylococcal Enterotoxins 

Commenters to the July 21, 2010 

ANPRM suggested that the regulations 

needed a clear statement concerning 

staphylococcal enterotoxins (SEs) and 

staphylococcal enterotoxin-like toxins 

(SEls). Commenters stated that SEs and 

SEls have been distinguished from each 

other on the basis of emetic activity (Ref 

12). Commenters were confused 

regarding whether the intent of the 

select agent regulations is to 

acknowledge this difference and not 

regulate SEls or to regulate both SEs and 

SEls. 


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ISATTAC recommended that we 

amend the HHS list of select agents and 

toxins to specifically include 

Staphylococcal enterotoxins A, B, C, D, 

and E in the HHS list of select agents 

and toxins. We agree with the 

commenters and the ISATTAC 

recommendation, and propose to amend 

the select agents and toxins list from 

‘‘Staphylococcal enterotoxins’’ to 

specifically include ‘‘Staphylococcal 

enterotoxins A, B, C, D, and E’’ in the 

HHS list of select agents and toxins (Ref 

7–14). Serotypes G, H, and I should not 

added to the HHS list of select agents 

and toxins because serotypes G, H, and 

I are at least 10 fold less of a risk than 

SEE and SEA (Ref 15–16.) According to 

the International Nomenclature 

Committee for Staphylococcal 

Superantigens, emesis in a primate 

model within five hours post-feeding 

must be observed to classify an exotoxin 

as an enterotoxin (Ref 12). If emesis is 

not observed in this period of time, the 

exotoxin should be classified as 

enterotoxin-like rather than enterotoxin. 

Based on this internationally accepted 

standard, we are proposing serotypes J, 

K, L, M, N, O, P, Q, T, U, U2 and V 

should be designated staphylococcal 

enterotoxin-like rather than enterotoxin 

because these serotypes have been 

shown to either not cause emesis in a 

primate model or have not been tested 

for emesis (Ref 17–26). Therefore, we 

are proposing serotypes J, K, L, M, N, O, 

P, Q, T, U, U2 and V should not added 

to the HHS list of select agents and 

toxins. 

B. Modifications to the List of Overlap 

Select Agents and Toxins 

The following changes to the list of 

Overlap select agents and toxins are 

proposed based on comments received 

to the July 21, 2010 ANPRM, 

recommendations from the FESAP and 

ISATTAC, and our review of current 

scientific data regarding select agents 

and toxins. 

Proposed Retention of Bacillus 

anthracis (Pasteur Strain) 

A commenter to the July 21, 2010 

ANPRM stated that the Pasteur strain of 

Bacillus anthracis should not be 

considered a select agent because the 

strain is attenuated and used for quality 

control testing in Laboratory Response 

Network (LRN) laboratories. The 

commenter argued that changing the 

status of the Pasteur strain would 

alleviate the burden of recordkeeping 

for quality control and proficiency 

testing activities. 

We made no changes based on this 

comment. It should be noted that we 

excluded Bacillus anthracis Sterne 

strain in 2003 because the attenuated 

strain was determined to not pose a 

severe threat to public health and safety, 

animal health, or animal products. We 

have not excluded the plasmid-negative 

Pasteur variant in order to prevent the 

combination of plasmids from Sterne 

and Pasteur-types of strains to create a 

wild type phenotype. 

Proposed Retention of Brucella abortus, 

Brucella melitensis, and Brucella suis 

Commenters to the July 21, 2010 

ANPRM recommended that Brucella 

abortus, Brucella melitensis, and 

Brucella suis be removed from the 

Overlap list of select agents and toxins 

for the following reasons: 

• The benefits of removal far exceed 

any risk mitigated by continuing the 

listing. In the years since the organism 

was first listed, research and 

development has been greatly 

diminished. 

• As currently regulated, existing 

BSL–3 facilities do not have the 

capacity to conduct brucellosis research 

with sufficient numbers of animals to 

generate statistically valid research 

results, and it is too expensive to 

construct and maintain enough high 

capacity BSL–3 facilities to conduct the 

necessary research. The commenter 

contended that any risk currently 

mitigated by the listing is fully 

manageable without such listing. 

• Brucella abortus and Brucella suis 

should be removed because the 

organisms are adversely affected by 

environmental conditions and can be 

diagnosed and controlled in animals 

and readily treated in humans. The 

classification of these bacteria as select 

agents has hampered research that could 

result in vaccines that would protect 

susceptible animal populations. 

Although brucellosis will remain a 

disease of agricultural significance, 

Brucella abortus and Brucella suis are 

not ideal biological weapons. The 

commenter suggested, however, that 

Brucella melitensis remain on the list 

because it is a foreign animal disease 

and the most infectious of all the 

species. 

• Brucella species should have their 

listed status reconsidered because 

human infection is rarely fatal, acute 

brucellosis can be readily treated with 

available antibiotics, human-to-human 

transmission is extremely rare, and 

wildlife carriers in the United States 

often come into contact with humans 

without significant transmission. 

• Naturally occurring substances such 

as Brucella should be removed because 

infections regularly occur from natural 

exposures. 

• The primary mode of transmission 

for Brucella abortus is through contact 

with contaminated fluids/tissues, its 

pathogenicity is moderate, and 

infections are routinely treated with 

antibiotics that do an effective job. The 

commenter recommended removal of 

Brucella abortus strain 1119–3 because 

the strain is identical using 

conventional typing tests to strain 19 

and is used as an antigen strain in 

diagnostic tests. Strain 19 and RB51 

have been excluded as licensed vaccine 

products, but other research strains have 

not been excluded. 

• Another commenter supported 

downgrading the risk assessment for 

vaccine strains of Brucella. The 

commenter was concerned that the only 

criterion the ISATTAC accepts for 

exclusion is licensed drug status, but 

such a high standard is disadvantageous 

to research on this pathogen. 

The FESAP and ISATTAC 

recommended that Brucella abortus, 

Brucella melitensis, and Brucella suis 

remain on the Overlap list of select 

agents and toxins. We made no changes 

based on these comments because we 

agreed with these expert panels that 

Brucella abortus, Brucella melitensis, 

and Brucella suis remain on the Overlap 

list of select agents and toxins based on 

the bacteria’s ease of production, high 

infectivity via the aerosol route, low 

infectious dose, and no brucellosis 

vaccines are currently available for 

humans in the United States. 

Proposed Retention of Burkholderia 

mallei and Burkholderia pseudomallei 

Commenters to the July 21, 2010 

ANPRM contended that Burkholderia 

mallei and Burkholderia pseudomallei 

should not be included as select agents 

based on the following reasons: 

• The agents do not rise to the same 

level of public health threat or 

feasibility for weaponization that the 

other agents on the list do. 

• Burkholderia mallei and 

Burkholderia pseudomallei are endemic 

in a number of areas of the world. 

• Disease resulting from Burkholderia 

mallei and Burkholderia pseudomallei 

is treatable with low mortality. 

• It is questionable how they would 

be used as bioweapons. 

The FESAP and ISATTAC 

recommended that Burkholderia mallei 

and Burkholderia pseudomallei remain 

on the Overlap list of select agents and 

toxins. We made no changes based on 

these comments because we agreed with 

these expert panels that Burkholderia 

mallei and Burkholderia pseudomallei 

should remain on the Overlap list of 

select agents and toxins based on our 

scientific determination that the bacteria 


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can be produced in large quantity; 

transmitted via aerosol; and 

Burkholderia pseudomallei is highly 

stable in the environment. The mortality 

rate for untreated cases of both 

melioidosis and glanders is high, and 

given the rarity of these diseases in the 

United States, experience in their 

diagnosis and treatment is limited. 

Proposed Reorganization of Venezuelan 

Equine Encephalitis Virus (VEEV) 

Commenters to the July 21, 2010 

ANPRM contended that VEEV subtypes 

ID and IE should not be included as 

select agents based on the following 

reasons: 

• Inclusion of VEEV subtypes as 

select agents should be based solely on 

their ability to cause an epidemic or 

epizootic following a bioterrorism event. 

This would require inclusion of only 

varieties 1AB and 1C VEEV which have 

been shown to have epidemic/epizootic 

potential. 

• The reasons for excluding 1D and 

1E VEEVs from the select agent list are: 

(1) No subtype 1D or 1E VEEV have ever 

caused large equine epizootics; (2) 

Inclusion of 1D viruses because they 

might be precursors to 1C viruses is not 

sufficient for making 1D viruses select 

agents. Essentially all of this evidence is 

laboratory based. The possibility of a 1D 

virus mutating to a 1C virus following 

a bioterrorism event is unlikely because 

1D viruses are unlikely to establish 

epidemic or epizootic transmission 

cycles in the US. Natural transmission 

cycles would likely be needed for any 

evolution from 1D to 1C to occur in 

nature; (3) Emergency vaccination of 

equines with currently approved equine 

vaccines or humans with IND vaccines 

(e.g. TC–83) would interdict or greatly 

dampen a 1D or a 1E epizootic, based 

on antigenic cross-reactivities of 

subtype 1 viruses; and (4) The currently 

available humanized or human antiVEEV monoclonal antibodies that could 

be produced for emergency use would 

also have prophylactic, and possibly 

therapeutic efficacy for all VEEV 

subtype 1 infections with which they 

cross react (includes 1D and 1E viruses). 

The FESAP and ISATTAC 

recommended removal of certain 

subtypes of Venezuelan equine 

encephalitis virus from the Overlap list 

of select agents and toxins. Since we 

agreed with commenters and expert 

panels recommendations, we are 

proposing to clarify that only VEEV 

subtypes IAB and IC should remain on 

the Overlap list of select agents and 

toxins because these subtypes contain 

the only recognized strains of 

Venezuelan equine encephalitis that 

have demonstrated the ability to cause 

epidemics or epizootics. The remaining 

subtypes, ID and IE, are strains 

prevalent among the existing animal 

populations and do not represent the 

same type of risk. Other viruses within 

the Venezuelan equine encephalitis 

complex (subtypes IF and II through IV) 

are separate viruses and are not 

included in the HHS and USDA overlap 

list of select agents and toxins. 

C. Tiering 

E.O. 13546 specifies that a subset of 

the Select Agent List be categorized as 

‘‘Tier 1’’ because these agents and toxins 

present the greatest risk of deliberate 

misuse with the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence. All but one of the 

commenters to the July 21, 2010 

ANPRM who addressed the idea of a 

tiering system based on the relative 

bioterrorism risk of each agent or toxin 

favored the use of tiers. Several 

commenters mentioned specific criteria 

for tiering. A few commenters expressed 

the concern that tiering could create 

confusion, especially for facilities with 

multiple Biological Select Agents and 

Toxins (BSAT) and had concerns about 

additional requirements that would be 

placed on some laboratories. Some 

commenters identified specific Tier 1 

candidates from the BSAT listed in 42 

CFR 73.3 and § 73.4. Most of these 

commenters included Variola major 

virus and Variola minor virus, as well 

as Reconstructed 1918 Influenza virus, 

Ebola viruses, and Marburg virus in 

their Tier 1 list. Two commenters also 

suggested Bacillus anthracis and Lassa 

fever virus. Other commenters suggested 

Francisella tularensis, South America 

hemorrhagic fever viruses, Brucella 

species, Coxiella burnettii, Botulinum 

neurotoxin, and Ricin as candidates for 

Tier 1. 

Based on E.O. 13546, a FESAP 

recommendation and our agreement 

with the comments received, we are 

proposing to amend the select agent 

regulations to establish a number of 

select agents and toxins as Tier 1 select 

agents and toxins within the lists of 

HHS and Overlap select agents and 

toxins. All select agents and toxins were 

scored against 20 criteria by over 60 

Subject Matter Experts representing the 

Federal life sciences, public health, law 

enforcement, security, and intelligence 

communities, which included: 

• The relative ease with which a 

particular select agent or toxin might be 

disseminated or transmitted from one 

human to another or into the 

environment where it could produce a 

deleterious effect upon human health; 

• The potential for a high mortality 

rate; 

• The potential for a major human 

health impact; 

• Select agents or toxins whose 

misuse might result in public panic or 

other social or economic disruption; and 

• Select agents or toxins whose use 

might require Federal, State, and/or 

local officials to take special action in 

planning for major human health 

disasters. 

The select agents that we propose will 

be designated as Tier 1 are the 

following: 

HHS 

• Ebola virus 

• Francisella tularensis 

• Marburg virus 

• Variola major virus 

• Variola minor virus 

• Yersinia pestis 

• Botulinum neurotoxin 

• Toxin-producing strains of 

Clostridium botulinum 

OVERLAP 

• Bacillus anthracis 

• Burkholderia mallei 

• Burkholderia pseudomallei 

Regarding the Reconstructed 1918 

Influenza virus, recent studies have 

increased our understanding of the 

public health risks associated with this 

agent. Current reports indicate that 60 

percent of the population in the United 

States is immune to the 1918 Influenza 

virus and that antiviral treatments exist 

(Ref 27–28). Based on this information 

we propose to retain the Reconstructed 

1918 Influenza virus on the HHS list of 

select agents and toxins, but not to 

include it in Tier 1 of this list. 

Based on the information currently 

available, we conclude that the adoption 

of the Tier 1 designation would not 

result in significant economic effects to 

the regulated community. However, we 

are asking for any additional data or 

comments on the potential effects of 

designating the above agents as Tier 1. 

D. Responses to Other Comments and 

Other Proposed Changes 

With respect to the remainder of the 

sections outlined below, we are 

proposing the following changes based 

on comments received in response to 

the July 21, 2010 ANPRM and 

recommendations from the FESAP. We 

are proposing to update the Web 

address throughout the document as all 

information concerning the Federal 

Select Agent Program is now centralized 

on the National Select Agent Registry 

Web site at http://www.selectagents. 

gov/. We also are proposing nonsubstantive changes throughout the 


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regulations for purposes of clarity. In 

addition, HHS/CDC and USDA/APHIS 

made the language similar to ensure 

consistency between the regulations. 

Exclusions 

In order to update the regulations to 

accurately reflect the way in which we 

handle the listing of exclusions, we are 

proposing to remove the language 

stating that exclusions will be published 

in the Federal Register. This change is 

necessary because, while we anticipated 

publication of exclusions both in the 

Federal Register and on the Internet at 

the time the regulations were initially 

created, we have found that publication 

on the select agent Web site only has 

served to provide the most up-to-date 

information to the regulated 

community. 

Security 

Commenters that responded to the 

July 21, 2010 ANPRM suggested 

security requirements include 

laboratory handling only by certified, 

trained individuals; physical security 

systems; restricted access; and security 

risk assessments. Commenters also 

identified some criteria for stratifying, 

such as making the requirements riskbased, considering the type of work 

done at the facility, acknowledging that 

many threats are from disgruntled 

insiders, requiring review of the 

stratification by subject matter experts, 

and taking into account the needs of the 

researchers at the facility. 

Based on our agreement with the 

comments received, and input from the 

FESAP and stakeholder groups, we are 

proposing more specific minimum 

security standards for Tier 1 select 

agents or toxins. These additional 

requirements would be added as section 

73.11(e). We believe these proposed 

minimum security standards for Tier 1 

select agents would serve to further 

mitigate the potential for deliberate 

misuse of these select agents and toxins 

that could result in mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence. 

These proposed changes are based on 

established security industry standards 

with respect to securing high risk 

material and developed in accordance 

with the experience and expertise of the 

Federal Select Agent Program and in 

consultation with DOD, FBI, and DHS 

security experts. They are necessary in 

order to further ensure the safety and 

security of those select agents and 

toxins that are proposed to be deemed 

Tier 1 agents. The requirements for 

working with all other select agents and 

toxins would remain unchanged with 

the exception of certain miscellaneous 

changes that are detailed below. 

Security of Variola Major Virus and 

Variola Minor Virus 

In recognition of the special public 

health risks associated with Variola 

major virus and Variola minor virus, we 

are also proposing to require additional 

physical security measures over and 

above those proposed for Tier 1. These 

additional requirements would be 

added as section 73.11(e)(5) (Security). 

We believe this change is necessary 

because Variola major virus and Variola 

minor virus were determined to pose a 

significantly higher public health risk 

than the other agents and toxins that 

were proposed for the Tier 1 select 

agents and toxins list. We also believe 

that it would not be appropriate to 

require that the special security 

procedures appropriate for Variola 

major virus and Variola minor virus be 

made applicable to other agents or 

toxins on a Tier 1 list. 

Select Agent Inventory 

Many commenters to the July 21, 2010 

ANPRM pointed out that the 

requirement to account for individual 

vials of each pathogen is inappropriate 

for replicating biological agents. 

Commenters stated that this is a costly 

and burdensome responsibility for 

laboratories and their staff and that this 

requirement should be abolished except 

for Tier 1 agents. 

We are not proposing any changes to 

the select agent regulations based on 

these comments. Currently, the select 

agent regulations state that an accurate, 

current inventory for each select agent 

(including viral genetic elements, 

recombinant nucleic acids, and 

recombinant organisms) held in longterm storage (placement in a system 

designed to ensure viability for future 

use, such as in a freezer or lyophilized 

materials) must be maintained. The 

requirement to account for individual 

vials of each pathogen in long term 

storage is necessary to ensure the 

biosecurity of select agents and toxins. 

Further guidance on this requirement 

can be found at http:// 

www.selectagents.gov. 

Definitions 

In order to improve the clarity of the 

HHS Select Agent Regulations, we are 

proposing to add the following 

definitions to 42 CFR 73.1, to clarify the 

terms related to the identification of a 

Restricted person: Adjudicated as a 

mental defective, Alien, Crime 

punishable by imprisonment for a term 

exceeding 1 year, Committed to any 

mental institution, Controlled 

substance, Indictment, Information 

security; Lawfully admitted for 

permanent residence, Mental 

institution, and Unlawful user of any 

controlled substance. We believe that 

these definitions will assist Responsible 

Officials as well as those seeking 

approval to access select agents and 

toxins to better understand what status 

or activities, past or present, might 

prohibit such access. 

Although these terms were undefined 

in the Bioterrorism Response Act, it is 

evident that Congress modeled many of 

them after the disqualifiers that are used 

by the Bureau of Alcohol, Tobacco, 

Firearms, and Explosives (ATF) when 

enforcing the Gun Control Act of 1968. 

Because the purpose of the Select Agent 

Program differs from ATF’s enforcement 

actions under the Gun Control Act, we 

do not believe that these terms must be 

defined exactly the same. The Gun 

Control Act regulates access to firearms, 

while the Bioterrorism Response Act 

regulates access to biological agents and 

toxins that the government has 

recognized as having the potential to be 

used as weapons of mass destruction by 

the wrong hands. 

Nevertheless, we looked at the 

statutory and regulatory definitions of 

these terms under the Gun Control Act 

when drafting our definitions. With the 

exception of the term ‘‘crime punishable 

by imprisonment for a term exceeding 1 

year,’’ we decided to adopt the 

applicable definitions used by ATF. 

We are proposing to define a ‘‘crime 

punishable by imprisonment for a term 

exceeding 1 year’’ as ‘‘any Federal, 

State, or foreign offense for which the 

maximum penalty, whether or not 

imposed, is capital punishment or 

imprisonment in excess of 1 year. What 

constitutes a conviction of such a crime 

shall be determined in accordance with 

the law of the jurisdiction in which the 

proceedings were held. Any conviction 

that has been set aside or nullified as a 

matter of law or for which a person has 

been pardoned shall not be considered 

a conviction for purposes of this part.’’ 

Contrary to definition of this term used 

under the Gun Control Act, we have 

decided that foreign offenses should be 

considered a disqualifier. In doing so we 

are aware of the Supreme Court’s 

decision in Small v. United States, 544 

U.S. 385 (2005) in which the court, 

interpreting the provisions of 18 U.S.C. 

922(g)(1), held that phrase ‘‘convicted in 

any court’’ refers only to U.S. courts, not 

to foreign courts. In its opinion 

interpreting the Gun Control Act, the 

court stated that ‘‘the statute itself and 

its history offer only congressional 

silence’’ as to whether Congress 

considered whether the statutory 


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language included foreign convictions. 

In the case of the Public Health Security 

and Bioterrorism Preparedness and 

Response Act of 2002 (Bioterrorism and 

Response Act), we believe Congress 

spoke clearly about their desire to limit 

or deny access to select agents and 

toxins for those who have committed 

serious crimes regardless of where 

committed. 

We believe that in light of the threat 

of bioterrorism attacks, Congress would 

not want to exclude an individual 

convicted of a U.S. offense from having 

access to BSAT, but still allow access to 

an individual convicted in a foreign 

court of a similar offense. 

As a part of the safeguard and security 

section of the Bioterrorism Response 

Act, Congress not only put select agents 

and toxins off limits to a ‘‘restricted 

person,’’ as that term is defined by 18 

U.S.C. 175b, but to those who are 

‘‘reasonably suspected by any Federal 

law enforcement or intelligence agency 

of’’ (1) committing a ‘‘Federal crime of 

terrorism’’ transcending national 

boundaries (18 U.S.C. 2332b), (2) the 

knowing involvement with an 

organization that engages in domestic or 

international terrorism or with any other 

organization that engages in 

international crimes of violence; or (3) 

being an agent of a foreign power. We 

believe it would be an inconsistent 

reading of statutory authority to allow 

the Secretary to limit or deny access to 

select agents and toxins to someone 

identified by the Attorney General as 

being reasonably suspected of 

committing a Federal crime of terrorism 

transcending national boundaries but to 

be powerless in cases where a person 

had actually been convicted of a serious 

crime in a foreign country. We also 

believe that the instances of regulation 

can be distinguished in that with regard 

to the Gun Control Act of 1968, the 

government is regulating access to guns 

while with respect to the Bioterrorism 

Response Act, the government is 

regulating access to biological agents 

and toxins that the government has 

recognized as having the potential to be 

used in the wrong hands as weapons of 

mass destruction. 

We specifically request comments on 

the use of a foreign conviction as a 

predicate for denying access to select 

agents and toxins. We recognize that 

there can be significant differences 

between foreign convictions and 

domestic convictions. For example, 

foreign legal systems may not provide 

the same due process safeguards 

afforded to citizens of the United States, 

including impartial tribunals and jury 

trials. Additionally, foreign countries 

may punish conduct that is permitted 

under domestic law or may require 

more severe penalties than under 

domestic law. We note that in the past, 

courts have applied the criteria set forth 

in Section 482 of the Restatement (third) 

of Foreign Relations Law of the United 

States (1986) in determining whether a 

foreign judgment should be recognized 

in the United States. That Section 

provides that a court in the United 

States may not recognize a judgment of 

the court of a foreign state if the 

judgment was rendered under a judicial 

system that does not provide impartial 

tribunals or procedures compatible with 

due process of law or the court that 

rendered the judgment did not have 

jurisdiction over the defendant in 

accordance with the law of the 

rendering state. It further provides that 

a court in the United States need not 

recognize a judgment of the court of a 

foreign state if the court that rendered 

the judgment did not have jurisdiction 

of the subject matter of the action, the 

defendant did not receive notice of the 

proceedings in sufficient time to enable 

him to defend, the judgment was 

obtained by fraud, the cause of action on 

which the judgment was based, or the 

judgment itself, is repugnant to the 

public policy of the United States or of 

the State where recognition is sought, 

the judgment conflicts with another 

final judgment that is entitled to 

recognition, or the proceeding in the 

foreign court was contrary to an 

agreement between the parties to submit 

the controversy on which the judgment 

is based to another forum. We are 

seeking comment on whether these 

criteria should be applied in 

considering whether access to select 

agents and toxins should be denied 

based on a foreign conviction or 

whether other criteria or factors would 

be appropriate to consider. 

Also, contrary to the definition used 

by ATF, we are proposing that a state 

offense classified by the laws of that 

state as a misdemeanor, but which has 

a term of imprisonment exceeding one 

year, should be considered a 

disqualifier—even though an individual 

convicted of the same offense would not 

be disqualified under the Gun Control 

Act. Finally, we are proposing to permit 

access to BSAT to individuals who have 

been convicted of a disqualifying 

offense if their convictions have been 

set aside or nullified as a matter of law 

or they have been pardoned. Although 

such language was not specifically 

included in the Bioterrorism Response 

Act, we believe that we should take into 

account certain post-conviction actions 

when determining whether we should 

deny an individual access to BSAT. 

We are proposing to add a definition 

for Occupational exposure based on the 

definition used in the Occupational 

Safety and Health Administration 

(OSHA) regulations found in 29 CFR 

1910.1030. In addition, we are 

proposing to add the definitions for 

Recombinant and Synthetic Nucleic 

Acids to clarify the existing regulations, 

as the term ‘‘recombinant nucleic acids’’ 

is employed but not defined, and 

synthetic nucleic acids are not currently 

addressed in the HHS Select Agent 

Regulations. 

Recombinant/Synthetic Nucleic Acids 

In addition to adding the proposed 

definition for Recombinant and 

Synthetic Nucleic Acids, we are also 

proposing to add the phrase ‘‘and/or 

synthetic’’ after the word 

‘‘Recombinant’’ throughout 73.3 (c) and 

73.4 (c). Current regulations regarding 

recombinant nucleic acids and 

recombinant organisms focus solely on 

the use of recombinant technology in 

the generation of these genetic elements. 

Since synthetic DNA technology may 

also be used to generate such genetic 

elements, we are proposing to expand 

the category of genetic elements to 

include recombinant and/or synthetic 

DNA. 

Toxins 

Sections in §§ 73.3 and 73.4 of 42 CFR 

contain provisions for toxins regulated 

by HHS under part 73. In 42 CFR 73.3(e) 

and 73.4(e), we are proposing to clarify 

that the ‘‘inactive form of a select toxin’’ 

may be excluded from regulation since 

the current term, ‘‘attenuated strain of 

toxin’’ is scientifically inaccurate. 

‘‘Attenuated’’ is a term that is applied to 

living organisms and toxins are not 

living organisms. Since ‘‘Inactive form 

of a select toxin’’ is a more accurate 

term, we are proposing to amend the 

regulations to include the correct 

terminology. 

Section 42 CFR 73.3(d)(3) specifies 

the permissible select toxin amounts 

under the control of a principal 

investigator, treating physician or 

veterinarian, or commercial 

manufacturer or distributor that are 

excluded from the requirements of the 

select agent regulations. We are 

proposing to require that the person 

transferring toxins in amounts which 

would otherwise be excluded from the 

provisions of the select agent 

regulations would be excluded only if 

the transferor: (1) Can show that the 

transferor used due diligence (i.e., 

reasonably justified by a prophylactic, 

protective, bona fide research, or other 

peaceful purpose) to assure that the 

recipient has a legitimate need to handle 


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or use such toxins; and (2) reports to 

CDC if they detect a known or suspected 

violation of Federal law or become 

aware of suspicious activity related to 

the toxin. The HHS Secretary would 

also retain the authority to, without 

prior notification, inspect and copy or 

request the submission of the due 

diligence documentation. It should be 

noted that this proposed requirement 

would not apply to toxins exempted 

under Section 42 CFR 73.5(c). 

We are proposing to add 42 CFR 

73.3(d)(4) which would state, 

‘‘Notwithstanding section (i) above, an 

animal inoculated with or exposed to an 

HHS select toxin.’’ The current 

regulations consider that an animal 

injected with or exposed to (e.g., by 

inhalation, dermal absorption, or 

ingestion) a select toxin is a ‘‘select 

toxin’’ itself and would need to be 

housed in a registered space. This 

change would allow animals injected 

with or exposed to a select toxin to not 

be considered a ‘‘select toxin.’’ 

Therefore, the animals would not need 

to be housed in a registered space. This 

change will eliminate an unnecessary 

burden on a registered entity because 

recovering the toxin from within an 

animal subject is highly difficult and 

such removal is unlikely to produce a 

reasonable yield of recovery. In 

addition, there is uncertainty as to 

whether the toxin would remain active 

when recovered from the animal. For 

these reasons, it is highly unlikely that 

once introduced into an animal, 

sufficient toxin would be able to be 

recovered to pose a significant hazard to 

public health. 

Exemptions 

The regulations found in 42 CFR 73.5 

and 73.6 requires identified select 

agents listed on the CDC’s Category A 

Bioterrorism Agents list (i.e., agents that 

pose a risk to national security because 

they can be easily disseminated or 

transmitted from person to person; 

result in high mortality rates and have 

the potential for major public health 

impact; might cause public panic and 

social disruption; and require special 

action for public health preparedness) 

contained in a specimen presented for 

diagnosis or verification to be 

immediately reported to APHIS or CDC 

by telephone, facsimile, or e-mail. 

We are proposing to amend this 

immediate notification to only those 

select agents and toxins identified as 

Tier 1 agents because these agents and 

toxins present the greatest risk of 

deliberate misuse with the most 

significant potential for mass casualties. 

Responsible Official 

The regulations found in 42 CFR 73.9 

set out requirements for entities 

requesting to work with select agents 

and toxins to designate a Responsible 

Official, who ensures that the entity 

meets the requirements of the 

regulations. 

We are proposing to add a specific 

requirement that all Responsible 

Officials possess the appropriate 

training or expertise to execute their 

required duties. We are also proposing 

to add a requirement that the 

Responsible Official’s regular place of 

employment or principal duty station 

must be collocated in close proximity 

with the physical location of the 

registered entity entered in section 1A 

of APHIS/CDC Form 1 (Application for 

Registration for Possession, Use, and 

Transfer of Select Agents and Toxins 

OMB Control No. 0579–0213, OMB 

Control No. 0920–0576, Expiration Date 

12/31/2011). We believe that the 

Responsible Official should have a 

physical (and not merely a telephonic or 

audio/visual) presence at the entity to 

ensure that the entity is in compliance 

with the select agent regulations and be 

able to quickly respond to on-site 

incidents involving select agents and 

toxins. 

We are also proposing to clarify the 

role of Alternate Responsible Official in 

order to definitively establish that the 

Alternate Responsible Official must 

have the knowledge and authority to act 

for the Responsible Official in his/her 

absence. 

Access to Select Agents and Toxins 

We are proposing to amend the 

regulations in 42 CFR 73.10. These 

regulations establish parameters for 

restricting access to select agents and 

toxins and the process by which 

individuals may be approved by HHS/ 

CDC or USDA/APHIS for access to 

select agents and toxins after the 

completion of a security risk assessment 

by the Attorney General. Specifically, 

we are proposing to add new provisions 

by which individuals may have access 

to select agents and toxins at entities 

other than the individual’s ‘‘home’’ 

entity. 

We are also proposing to decrease the 

maximum length of time in which a 

security risk assessment will be valid 

from five years to three years in order 

to more expeditiously identify 

individuals who may have fallen into 

one of the prohibited or restricted 

categories. 

Security Plan 

The regulations in 42 CFR 73.11 

establish the requirements for 

developing and implementing a security 

plan sufficient to safeguard select agents 

or toxins against unauthorized access, 

theft, loss, or release. The regulations 

currently require that the security plan 

must be submitted by all regulated 

entities upon request. We are proposing 

to amend § 73.11 to require that the 

security plan be submitted for initial 

registration and renewals of registration. 

Since we believe animals and plants 

exposed to or infected with a select 

agent should be handled as a select 

agent and safeguarded in the same 

manner as a select agent, we are 

proposing to require that the security 

plan include provisions to address 

safeguarding of animals or plants 

intentionally or exposed to or infected 

with select agents against unauthorized 

access, theft, loss or release. We are not 

requiring this plan to address 

procedures concerning animals exposed 

to toxins because, as discussed above, it 

is highly unlikely that once introduced 

into an animal, sufficient toxin can be 

recovered to pose a significant hazard to 

public health and safety. We are 

additionally proposing to add a 

requirement that the security plan 

include procedures for the Responsible 

Official to immediately notify the 

Federal Bureau of Investigation (FBI) of 

suspicious activity that may be criminal 

in nature and related to the entity, its 

personnel, or its select agents or toxins. 

We believe that any criminal activity of 

this kind should be immediately and 

directly reported to the FBI so they can 

initiate an investigation or other 

appropriate response. 

We are proposing that the security 

plans of entities with select agents and 

toxins must include provisions for 

information security. These information 

security provisions would include 

network connectivity monitoring, 

restriction of user permissions so that 

only mission-specific files and 

applications may be accessed, measures 

to prevent network infiltration by 

malicious code, configuration 

management including regular patching 

and system and software updates, and 

backup security measures in the event 

that access control systems and/or 

surveillance devices are rendered 

inoperable. We believe that information 

security enhancements are important 

because the security of records or 

information systems that could allow an 

individual to gain access to the select 

agents or toxins should be safeguarded 

to prevent unauthorized access, theft, 

loss, or release of these materials. 

We are proposing to codify current 

practices for shipping, receiving, and 

storage of select agents and toxins to 

ensure that the entity has documented 


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processes for securing and monitoring 

the shipment, receipt, and storage of 

these items. These changes would serve 

to decrease the chance that such 

materials would be made available to an 

unauthorized individual or an 

individual without a legitimate use for 

the material. 

We are also proposing to remove the 

reference in 73.11(e), ‘‘Laboratory 

Security and Emergency Response 

Guidance for Laboratories Working with 

Select Agents’’ in Morbidity and 

Mortality Weekly Report (December 6, 

2002) because we posted a security 

information guidance document in 

March 2007 that supersedes this 

reference. 

Biosafety Plan 

We are proposing to amend the 

regulations in 42 CFR 73.12 to require 

that a regulated entity’s biosafety plan 

address procedures concerning animals 

or plants accidentally or intentionally 

exposed to or infected with a select 

agent. We are not requiring this plan to 

address procedures concerning animals 

exposed to toxins. As stated previously, 

this is because it is highly unlikely that 

once introduced into an animal, 

sufficient toxin can be recovered to pose 

a significant hazard to public health, 

agriculture or agriculture products. 

We are also proposing that the 

biosafety plan must include provisions 

for the implementation of an 

occupational health program for 

individuals with access to Tier 1 select 

agents and toxins. We believe aspects of 

an individual’s health may be relevant 

to their suitability to access biological 

select agents and toxins; identification 

of potential health problems and review 

of medication or treatment that may 

affect security and safety is paramount; 

and, occupational health programs 

should inform scientists of the types of 

medications and treatments that might 

have a potential deleterious effect on 

working safely and securely with select 

agents and toxins. 

Restricted Experiments 

The regulations in 42 CFR 73.13 

concern restricted experiments that may 

not be performed unless approved by 

the HHS Secretary. We are proposing to 

add language in order to expand the 

current ‘‘restricted experiment’’ 

approval requirement to include all 

experiments involving the creation of 

drug resistant select agents that are not 

known to acquire the resistance 

naturally, if such acquisition could 

compromise the use of the drug to 

control disease agents in humans, 

veterinary medicine, or agriculture and 

not just those involving recombinant 

DNA. The regulations in 42 CFR 73.13 

concern restricted experiments which 

may not be performed unless approved 

by the HHS Secretary. Furthermore, we 

are proposing to state that, in addition 

to the existing prohibition on 

conducting restricted experiments 

without express approval, entities may 

not possess the products (i.e., creation 

of drug resistant select agents that are 

not known to acquire the resistance 

naturally, if such acquisition could 

compromise the use of the drug to 

control disease agents in humans, 

veterinary medicine, or agriculture, or 

recombinant and or synthetic DNA 

containing genes for the biosynthesis of 

select toxins lethal for vertebrates at an 

LD[50] < 100 ng/kg body weight 

resulting from restricted experiments) 

resulting from restricted experiments 

without the express approval of the 

HHS Secretary. We are also proposing to 

remove recombinant technology as the 

only determining factor for a restricted 

experiment. Current regulations 

regarding restricted experiments focus 

solely on the use of recombinant 

technology in the generation of drug 

resistant select agents or biosynthesis of 

toxins lethal to vertebrates. Since 

synthetic DNA technology or selection 

in sublethal exposures may also be used 

to generate such products, we are 

proposing to expand the category of 

restricted experiments to include 

passive selection, recombinant and/or 

synthetic DNA. 

Incident Response 

The regulations in 42 CFR 73.14 

contain requirements for development 

of incident response plans. We are 

proposing to specify that each entity’s 

incident response plan be based upon a 

site-specific risk assessment. We believe 

this change would further ensure the 

specificity and quality of the plan. In 

addition, we are proposing that the 

incident response procedures contain 

specific provisions concerning animals 

or plants accidentally or intentionally 

exposed to or infected with a select 

agent. We are not requiring this plan to 

address procedures concerning animals 

exposed to toxins. As stated previously, 

this is because it is highly unlikely that 

once introduced into an animal, 

sufficient toxin can be recovered to pose 

a significant hazard to public health, 

agriculture or agriculture products. 

Training 

We are proposing to amend the 

regulations in 42 CFR 73.15 that contain 

provisions of mandatory training for 

staff and visitors who work in or visit 

areas where select agents or toxins are 

handled or stored to provide security 

awareness and incident response 

training. We believe these additional 

training initiatives are needed to ensure 

that (1) personnel will be better trained 

to safeguard select agents and toxins 

from thefts, losses, intentional releases, 

or unauthorized access and (2) 

personnel will be better trained to 

ensure that select agents and toxins are 

safeguarded during exigent 

circumstances that include natural and 

man-made disasters. We are also 

proposing to clarify the language 

regarding the level of training that staff 

and visitors would be required to 

receive in order to establish that training 

for escorted personnel based on the risk 

associated with accessing areas where 

select agents and toxins are used and/ 

or stored. Currently, refresher training is 

required to be provided once a year. We 

are proposing to require that such 

training also be provided if a registered 

entity’s security, incident response, or 

biosafety plans are substantively altered. 

Finally, we are proposing to specify that 

the Responsible Official ensure 

maintenance of training records. 

Currently, there is no particular person 

designated as the entity’s required 

record keeper, only that a training 

record must be kept. 

Transfers 

The transportation in commerce of 

hazardous materials, including select 

agents and toxins, is governed by the 

United States Department of 

Transportation’s Hazardous Material 

Regulations found in Title 49 of the 

Code of Federal Regulations, parts 100– 

185. The regulations in 42 CFR 73.16 do 

not impose requirements on the 

transportation in commerce of select 

agents or toxins. We are proposing to 

clarify when ‘‘transportation in 

commerce’’ begins and ends to better 

allow registered individuals and entities 

to adequately address those situations 

when a select agent or toxin is (1) ready 

to be packaged for transportation, (2) 

packaged for shipment, or (3) received 

and handled by a person with approval 

to access select agents and toxins. In 

addition, we are proposing language to 

codify policies and practices into a 

standard for shipping, receiving, and 

storage of select agents and toxins to 

ensure that the entity has documented 

processes for securing and monitoring 

the shipment, receipt, and storage of 

select agents and toxins that make it 

extremely unlikely that such materials 

would be made available to an 

unauthorized individual or an 

individual without a legitimate use for 

the material. We note the concerns 

identified in two HHS Office of 

Inspector General (OIG) audits regarding 


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vulnerabilities that may occur during 

the shipment of select agents and toxins. 

HHS/CDC reviewed how entities ship 

select agents and toxins and evaluated 

ways to improve this process to ensure 

they are not only safeguarded against 

unauthorized access, but also against 

theft, loss, or release. We believe that 

the proposed amendments will help 

address OIG’s concerns. 

Records 

The regulations in 42 CFR 73.17 

address recordkeeping requirements for 

regulated entities as those records that 

relate to select agents and toxins. We are 

proposing to clarify the current language 

that an accurate, current inventory 

needs to be maintained for each select 

agent that the entity possesses including 

synthetic select agent organisms and 

any animals or plants intentionally or 

unintentionally exposed to or infected 

with a select agent (including number 

and species, location and appropriate 

disposition). We believe this 

clarification is needed to ensure that 

accurate, current records are maintained 

for all select agents that the entity 

possesses. We are currently soliciting 

comments from the public (as well as 

affected agencies) concerning our 

proposed information collection and 

recordkeeping requirements. Please 

send written comments to Daniel 

Holcomb, CDC Acting Reports Clearance 

Officer, 1600 Clifton Road, MS–D74, 

Atlanta, GA 30333 or send an e-mail to 

omb@cdc.gov. Please state that your 

comments refer to Possession, Use, and 

Transfer of Select Agents and Toxins 

(OMB Control No. 0920–0576). 

As previously stated, we are not 

proposing to require regulated entities 

to keep records regarding animals 

exposed to toxins because it is highly 

unlikely that once introduced into an 

animal, sufficient toxin can be 

recovered to pose a significant hazard to 

public health, agriculture or agriculture 

products. 

Administrative Review 

We are proposing to amend the 

regulations in 42 CFR 73.20 that 

addresses the administrative review of 

an individual or entity’s denial, 

revocation, or suspension of registration 

and access approval. Specifically, we 

are proposing to modify the current 

regulations in order to allow individuals 

more time to gather the necessary 

components of their appeal following 

the denial, limitation, or revocation of 

access approval. Currently, this process 

must be initiated in 30 calendar days. 

We are proposing to extend the deadline 

to 180 calendar days. We believe this 

change would provide individuals with 

sufficient time to gather all documents 

necessary to support an appeal. Finally, 

we are proposing to remove the 

provision ‘‘Where the denial, 

revocation, or suspension of an 

individual’s access approval is based 

upon identification by the Attorney 

General, the request for review will be 

forwarded to the Attorney General’’ to 

provide clarification that the decision 

regarding the appeal is determined by 

the HHS Secretary. 

Guidance Documents 

We are specifically requesting 

comments from the regulated 

community and any other interested 

persons on the development of one or 

more guidance documents that would 

serve to provide assistance in the 

interpretation of the select agent 

regulations. 

The areas where guidance documents 

may be developed in relation to the 

select agent regulations include, but are 

not limited to: 

1. Aspects of the required security 

plan. These may include, but are not 

limited to: 

• Standards for information security; 

• Development of suitability or 

personnel reliability practices, 

including pre-access and ongoing 

assessment processes of persons who 

will have access to Tier 1 select agents 

or toxins; 

• Procedures for the method by 

which an entity’s Responsible Official 

will coordinate his or her efforts with 

the entity’s safety and security 

professionals to ensure security of Tier 

1 select agents or toxins and have access 

to relevant information from all 

professionals dealing with biological 

select agents and toxins safety and 

security; 

• Development of a self- and peerreporting program to track incidents or 

conditions that could affect an 

individual’s ability to safely access or 

work with Tier 1 select agents and 

toxins; and 

• Layered physical security 

protection of assets for entities housing 

Tier 1 select agents and toxins. 

2. Aspects of the required biosafety 

plan, e.g., components of an 

occupational health program for 

individuals with access to Tier 1 select 

agents and toxins; and 

3. Aspects of the required training, 

e.g., best practices for development of a 

security awareness training program. 

We welcome public comment on the 

use of Web sites, articles, or other 

sources that may be used to develop 

such documents, in addition to 

suggestions as to what elements should 

be included as useful examples. These 

documents would serve as a resource to 

the regulated community as a whole. 

III. Required Regulatory Analyses 

a. Executive Orders 12866 and 13563 

Executive Orders 12866 and 13563 

direct agencies to assess all costs and 

benefits of available regulatory 

alternatives and, if regulation is 

necessary, to select regulatory 

approaches that maximize net benefits 

(including potential economic, 

environmental, public health and safety 

effects, distributive impacts, and 

equity). E.O. 13563 emphasizes the 

importance of quantifying both costs 

and benefits, of reducing costs, of 

harmonizing rules, and of promoting 

flexibility. 

Under E.O. 12866 HHS must 

determine whether a regulatory action is 

‘‘significant.’’ A ‘‘significant regulatory 

action’’ under E.O. 12866 is defined as 

(1) an action that is likely to result in 

a rule that may have an annual effect on 

the economy of $100 million or more, or 

adversely and materially affects a sector 

of the economy, productivity, 

competition, jobs, the environment, 

public health or safety, or state, local or 

tribal governments or communities (or 

an economically significant action); 

(2) creates a serious inconsistency or 

otherwise interferes with an action 

taken or planned by another agency; 

(3) materially alters the budgetary 

impact of entitlements, grants, user fees 

or loan programs or the rights and 

obligations of recipients; or (4) raises 

novel legal or policy issues. Because 

this rulemaking proposes changes to 

how a subset of select agents and toxins 

are protected, this rule is has been 

determined to be ‘‘significant’’ under 

E.O. 12866 and, therefore, has been 

reviewed by the Office of Management 

and Budget (OMB). 

We have prepared an economic 

analysis for this rule. The economic 

analysis provides a cost-benefit analysis, 

as required by E.O. 12866, and an initial 

regulatory flexibility analysis (See III.b.) 

that examines the potential economic 

effects of this proposed rule on small 

entities, as required by the Regulatory 

Flexibility Act. The economic analysis 

is summarized below. Copies of the full 

analysis are available by contacting the 

person listed under FOR FURTHER

INFORMATION CONTACT or on the Federal 

Select Agent Program Web site at: 

http://www.selectagents.gov/ or on the 

public docket at http:// 

www.regulations.gov. 


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61218 Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 

Summary of the Regulatory Impact 

Analysis 

Certain pathogens or biological toxins 

that are released intentionally or 

accidentally can result in disease, wideranging and devastating impacts on the 

economy, disruption to society, 

diminished confidence in public and 

private institutions, and large-scale loss 

of life. People or livestock can be 

exposed to these agents from inhalation, 

through the skin, or by the ingestion of 

contaminated food, feed, or water. 

Similarly, crops can be exposed to 

biological pathogens in several ways—at 

the seed stage, in the field, or after 

harvest. 

The Public Health Security and 

Bioterrorism Preparedness and 

Response Act of 2002 (Pub. L. 107–188) 

(the Act) provides for the regulation of 

certain biological agents and toxins that 

have the potential to pose a severe 

threat to both human and animal health, 

to plant health, or to animal and plant 

products. APHIS and CDC have the 

primary responsibility for implementing 

the provisions of the Act within USDA 

and HHS, respectively. Within APHIS, 

Veterinary Services (VS) select agents 

and toxins are those that have been 

determined to have the potential to pose 

a severe threat to animal health or 

animal products, and Plant Protection 

and Quarantine (PPQ) select agents and 

toxins are those that have been 

determined to have the potential to pose 

a severe threat to plant health or plant 

products. HHS select agents and toxins 

are those that have been determined to 

have the potential to pose a severe 

threat to human health. APHIS and CDC 

coordinate regulatory activities for 

overlap select agents and toxins that 

have been determined to pose a severe 

threat to human and to animal health or 

animal products. 

Sections 201 and 212(a)(2) of the Act 

requires a biennial review and 

republication of the select agent and 

toxin list, with revisions as appropriate 

in accordance with this law. See 

42 U.S.C. 262a(a)(2) and 7 U.S.C. 

8401(a)(2), respectively. This rule would 

implement the recommendations of the 

third biennial review of the list. 

Furthermore, revision of these 

regulations would incorporate the 

recommendations developed as a result 

of E.O. 13546, ‘‘Optimizing the Security 

of Biological Select Agents and Toxins 

in the United States,’’ which requires 

that the HHS and USDA Secretaries 

publish proposed regulations to 

establish risk-based tiering of the select 

agent list, and revise the regulations, 

rules, and guidance to accommodate a 

tiered select agent list no later than 

October 2011. 

In addition, we are proposing several 

amendments to the regulations, 

including the addition of definitions 

and clarification of language concerning 

security, training, biosafety/ 

biocontainment, and incident response. 

These changes would increase the 

applicability and effectiveness of the 

select agent regulations and provide for 

enhanced program oversight. This rule 

would update the USDA, HHS, and 

overlap select agent and toxin lists. The 

regulation of select agents and toxins is 

intended to prevent their misuse and 

thereby reduce the potential for those 

pathogens to harm humans, animals, 

animal products, plants or plant 

products in the United States. Should 

any select agent or toxin be 

intentionally or unintentionally released 

into the environment, the consequences 

would be significant. Consequences 

could include disruption of markets, 

difficulties in sustaining an adequate 

food and fiber supply, and the potential 

spread of disease infestations over large 

areas. The entities most likely to be 

affected by this rule would be those 

laboratories and other institutions 

conducting research and related 

activities that involve the use of the 

newly categorized Tier 1 select agents 

and toxins. The impact of the changes 

to the regulations is expected to be 

minimal. Based on information obtained 

through site-specific inspections, we 

believe that very few entities would 

incur significant costs for compliance. 

Many of the proposed changes to the 

regulations would impose an added 

time cost to measures already required 

for compliance, with respect to security, 

biocontainment/biosafety, and incident 

response plans, information security, 

and ongoing background checks. While 

the total cost of the proposed 

regulations is estimated to range 

between $4.9 million and $6.4 million, 

we believe many of these costs are 

currently incurred by affected entities as 

generally recognized practices. Costs 

actually incurred would depend upon 

the number of computers and facility 

systems that require the proposed 

enhanced security. The expected 

benefits of strengthened safeguards 

against the unintentional or deliberate 

release of a select agent or toxin exceed 

the estimated costs of the proposed 

measures. Based on the information we 

have, there is no reason to conclude that 

adoption of this proposed rule would 

result in any significant economic effect 

on a substantial number of small 

entities. The entities are those 

laboratories and other institutions 

conducting research and related 

activities entities in possession of Tier 

1 select agents or toxins, and, to a 

somewhat lesser extent, those entities 

possessing the newly added select 

agents and toxins. The economic 

analysis presents categories and 

information from the Department of 

Commerce and the Small Business 

Administration for those entities we 

have identified as most likely to be 

affected by this rule. While we believe 

affected entities are contained within 

these categories, we are seeking further 

information regarding how many 

entities fall specifically into each 

category, and are therefore, inviting 

comments on potential effects. In 

particular, we are interested in 

determining the number and kind of 

small entities that may incur benefits or 

costs from the implementation of this 

proposed rule. 

This proposed rule would update the 

APHIS, CDC, and overlap select agent 

and toxin lists. The regulation of select 

agents and toxins is intended to prevent 

their misuse and thereby reduce the 

potential for those pathogens to harm 

humans, animals, animal products, 

plants or plant products in the United 

States. Should any select agent or toxin 

be intentionally or unintentionally 

released into the environment, the 

consequences would be significant. 

Consequences could include disruption 

of markets, difficulties in sustaining an 

adequate food and fiber supply, and the 

potential spread of disease infestations 

over large areas. The entities most likely 

to be affected by this rule would be 

those laboratories and other institutions 

conducting research and related 

activities that involve the use of the 

newly categorized Tier 1 select agents 

and toxins. The impact of the changes 

to the regulations is expected to be 

minimal, however. Based on 

information obtained through sitespecific inspections, indications are that 

very few entities would incur significant 

costs for compliance. Many of the 

proposed changes to the regulations 

would impose an added cost of the time 

spent on documenting measures already 

required for compliance, with respect to 

security, biocontainment/biosafety, and 

incident response plans, information 

security, and ongoing background 

checks. While the total costs imposed by 

the proposed regulations are estimated 

to range between $5.30 million and 

$6.95 million, including costs to 

government, we believe many of these 

costs are incurred through observance of 

generally recognized industry standards. 

Costs actually incurred would depend 

upon the extent to which current facility 


srobinson on DSK4SPTVN1PROD with PROPOSALS2
Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 61219 

practices will need to be enhanced 

based on the proposed requirements. 

The expected benefits of strengthened 

safeguards against the costs associated 

with unintentional or deliberate release 

of select agents or toxins would greatly 

exceed the estimated costs of the 

proposed measures. The cost associated 

with a single outbreak have been known 

to exceed $100 million as outlined in 

the Regulatory Impact Analysis. 

Deliberate introduction greatly increases 

the probability of a select agent or toxin 

becoming established and causing wideranging and devastating impacts on an 

economy, loss of market access for 

consumer goods and services, 

disruption to society, and diminished 

confidence in public and private 

institutions. 

This analysis reviews expected 

benefits and costs of the proposed rule 

in accordance with Executive Orders 

12866 and 13563. Possible impacts for 

small entities are also considered as 

required by the Regulatory Flexibility 

Act, which requires agencies to prepare 

and make available for public comment 

an initial regulatory flexibility analysis 

that describes expected impacts of a 

proposed rule on small businesses, 

small organizations and small 

governmental jurisdictions. 

Based on the information we have, 

there is no reason to conclude that 

adoption of this proposed rule would 

result in any significant economic effect 

on a substantial number of small 

entities. However, we do not currently 

have all of the data necessary for a 

comprehensive analysis of the effects of 

this proposed rule on small entities. 

Therefore, we are inviting comments on 

potential effects. In particular, we are 

interested in determining the number 

and kind of small entities that may 

incur benefits or costs from the 

implementation of this proposed rule. 

b. Regulatory Flexibility Act 

The Regulatory Flexibility Act (RFA) 

(5 U.S.C. 601 et seq.) requires an agency 

to consider the potential impact of its 

regulations on small entities, including 

small businesses, small governmental 

units, and small not-for-profit 

organizations. We certify that this rule 

will not have a significant economic 

impact on a substantial number of small 

entities within the meaning of the RFA. 

Therefore, a regulatory flexibility 

analysis as provided for under the RFA 

is not required. 

c. Paperwork Reduction Act of 1995 

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 proposed 

rule have been submitted for approval to 

the Office of Management and Budget 

(OMB). Please send written comments 

to the Office of Information and 

Regulatory Affairs, OMB, Attention: 

Desk Officer for APHIS, Washington, DC 

20503. Please state that your comments 

refer to Docket Nos. APHIS–2009–0070 

and CDC–2011–0012. Please send a 

copy of your comments to: (1) Docket 

Nos. APHIS–APHIS–2009–0070 and 

CDC–2011–0012, Regulatory Analysis 

and Development, PPD, APHIS, Station 

3A–03.8, 4700 River Road Unit 118, 

Riverdale, MD 20737–1238, and (2) 

Clearance Officer, OCIO, USDA, room 

404–W, 14th Street and Independence 

Avenue, SW., Washington, DC 20250. A 

comment to OMB is best assured of 

having its full effect if OMB receives it 

within 30 days of publication of this 

proposed rule. 

The Bioterrorism Preparedness Act is 

designed to prevent, prepare for and 

respond to bioterrorism and other 

public health emergencies. The law 

requires individuals possessing agents 

or toxins deemed a severe threat to 

human, animal, or plant health, or to 

animal or plant products, to be 

registered with the Secretary of 

Agriculture or the Secretary of Health 

and Human Services, unless they have 

been specifically exempted. 

This proposed rule entails the use of 

a number of separate forms designed to 

obtain critical information concerning 

individuals or entities in possession of 

certain agents or toxins, as well as the 

specific characteristics of the agents or 

toxins—including name, strain, and 

genetic information. This data is 

needed, in part, to allow APHIS and 

CDC to determine the biosafety level of 

an entity as well as the entity’s 

biosecurity situation. This, in turn, 

helps APHIS and CDC ensure that 

appropriate safeguard, containment, and 

disposal requirements commensurate 

with the risk of the agent or toxin are 

present at the entity, thus preventing 

access to such agents and toxins for use 

in domestic or international terrorism. 

Facilities containing select agents will 

be required to maintain records on 

animals and plants, and revise their 

Biosafety/Biocontainment Plan and 

Incident Response Plan for review by 

APHIS and CDC upon request. 

Information to determine that 

individuals seeking to register have a 

lawful purpose to possess, use, or 

transfer agents or toxins will also be 

requested as part of the registration 

process. In addition, we will be 

requesting submission of their Security 

Plan for our review. 

APHIS and CDC are asking OMB to 

approve, for 3 years, the use of these 

information collections, associated with 

its efforts to more closely regulate select 

agents or toxins that could be used to 

commit acts of domestic or international 

terrorism. We are soliciting comments 

from the public (as well as affected 

agencies) concerning this information 

collection activity. APHIS and CDC 

need this outside input to help 

accomplish the following: 

(1) Evaluate whether the proposed 

information collection is necessary for 

the proper performance of our agency’s 

functions, including whether the 

information will have practical utility; 

(2) Evaluate the accuracy of our 

estimate of the burden of the proposed 

information collection, including the 

validity of the methodology and 

assumptions used; 

(3) Enhance the quality, utility, and 

clarity of the information to be 

collected; and 

(4) Minimize the burden of the 

information collection on those who are 

to respond (such as through the use of 

appropriate automated, electronic, 

mechanical, or other technological 

collection techniques or other forms of 

information technology; e.g., permitting 

electronic submission of responses). 

Estimate of burden: Public reporting 

burden for this collection of information 

is estimated to average 2.3187883 hours 

per response. 

Respondents: Researchers, 

universities, research and development 

organizations, commercial 

manufacturers, non-profit institutions, 

diagnostic laboratories and other 

interested parties who possess, use, or 

transfer agents or toxins deemed a 

severe threat to human, animal or plant 

health, or to animal or plant products. 

Estimated annual number of 

respondents: 386. 

Estimated annual number of 

responses per respondent: 12.230569. 

Estimated annual number of 

responses: 4,721. 

Estimated total annual burden on 

respondents: 10,947 hours. (Due to 

averaging, the total annual burden hours 

may not equal the product of the annual 

number of responses multiplied by the 

reporting burden per response.) 


srobinson on DSK4SPTVN1PROD with PROPOSALS2
61220 Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 

Section Form name Number of 

respondents 

Number of 

responses per 

respondent 

Average 

burden per 

response 

(in hours) 

Total 

burden 

hours 

9 CFR 121.5 and 6, 7 CFR 331.5, 

43 CFR 73.5 and 6.

Report of Identification of a Select 

Agent or Toxin.

161 3 1 299 

§ 121.7, § 331.7, § 73.7 ..................... Application for Registration .............. 7 1 5 35 

§ 121.7, § 331.7, § 73.7 ..................... Amendment to a Certificate of Registration.380 7 1 1,955 

§ 121.11, § 331.11, § 73.11 ............... Security Plan .................................... 380 1 5 1,900 

§ 121.12, § 331.12, § 73.12 ............... Biosafety/Biocontainment Plan ........ 380 1 8 3,040 

§ 121.13, § 331.13, § 73.13 ............... Request Regarding a Restricted Experiment.160 1 2 320 

§ 121.14, § 331.14, § 73.14 ............... Incident Response Plan ................... 380 1 5 1,900 

§ 121.15, § 331.15, § 73.15 ............... Training ............................................ 380 1 1 380 

§ 121.16, § 331.16, § 73.16 ............... Request to Transfer Select Agents 

and Toxins.

290 1 2 580 

§ 121.17, § 331.17, § 73.17 ............... Records ............................................ 295 1 0.5 148 

§ 121.19, § 331.19, § 73.19 ............... Notification of Theft, Loss, or Release.195 1 2 390 

Copies of this information collection 

can be obtained from Mrs. Celeste 

Sickles, APHIS’ Information Collection 

Coordinator, at (301) 851–2908. 

d. Executive Order 12988: Civil Justice 

Reform 

This proposed rule has been reviewed 

under E.O. 12988, Civil Justice Reform. 

If this proposed rule is adopted: (1) All 

State and local laws and regulations that 

are inconsistent with this rule will be 

preempted; (2) no retroactive effect will 

be given to this rule; and (3) 

administrative proceedings will not be 

required before parties may file suit in 

court challenging this rule. 

e. Executive Order 13132: Federalism 

This rule has been reviewed under 

E.O. 13132, Federalism. The rule does 

not impose any regulation that would 

preempt State, local, and Indian Tribe 

requirements, or that would have any 

substantial direct effects on the States, 

or on the distribution of power and 

responsibilities among the various 

levels of government. 

f. Plain Writing Act of 2010 

Under Public Law 111–274 (October 

24, 2010), executive branch 

Departments and Agencies are required 

to use plain language in documents that 

explain to the public how to comply 

with a requirement the Federal 

Government administers or enforces. 

HHS has attempted to use plain 

language in promulgating the proposed 

rule consistent with the Federal Plain 

Writing Act guidelines. 

IV. References 

1. Delgado, Erickson, et al., 2008. Chapare 

virus, a newly discovered arenavirus 

isolated from a fatal hemorrhagic fever 

case in Bolivia. PLoS Pathogens 

4:e1000047. 

2. Briese T, Paweska JT, McMullan LK, 

Hutchison SK, Street C, Palacios G, 

Khristova ML, Weyer J, Swanepoel R, 

Egholm M, Nichol ST, Lipkin WI. 

Genetic detection and characterization of 

Lujo virus, a new hemorrhagic feverassociated arenavirus from southern 

Africa. PLoS 2009 May; 5(5):e1000455. 

Epub 2009 May 29. Available at http:// 

www.plospathogens.org. 

3. Galgiani, J.N. 1999. Coccidiomycosis: a 

regional disease of national importance. 

Ann Intern. Med. 130:293–298. 

4. Arrigo NC, Adams AP, Weaver SC. 

Evolutionary patterns of eastern equine 

encephalitis virus in North versus South 

America suggest ecological differences 

and taxonomic revision. J Virol. 2010 

Jan; 84(2):1014–25. 

5. Gresı ́kova ́ M, Kaluzova ́ M, 1997. Biology 

of tick-borne encephalitis virus. Acta 

Virol. Apr; 41(2):115–24. 

6. Ecker M, Allison SL, Meixner T, Heinz FX, 

1999. Sequence analysis and genetic 

classification of tick-borne encephalitis 

viruses from Europe and Asia. J Gen 

Virol. Jan; 80 (Pt 1):179–85. 

7. Bergdoll, M. S., 1988. Monkey feeding test 

for staphylococcal enterotoxin. Methods 

Enzymol 165: 324–33. 

8. Bergdoll, M. S., C. R. Borja, et al., 1971. 

Identification of enterotoxin E. Infect 

Immun 4(5): 593–5. 

9. Borja, C. R. and M. S. Bergdoll, 1967. 

Purification and partial characterization 

of enterotoxin C produced by 

Staphylococcus aureus strain 137. 

Biochemistry 6(5): 1467–73. 

10. Chintagumpala, M. M., J. A. Mollick, et 

al., 1991. Staphylococcal toxins bind to 

different sites on HLA–DR. J Immunol 

147(11): 3876–81. 

11. Chu, F. S., K. Thadhani, et al., 1966. 

Purification and characterization of 

staphylococcal enterotoxin A. 

Biochemistry 5(10): 3281–9. 

12. Lina, G., G.A. Bohach, et al., 2004. 

Standard nomenclature for the 

superantigens expressed by 

Staphylococcus. J Infect Dis 189(12): 

2334–6. 

13. Schantz, E.J., W.G. Roessler, et al., 1965. 

Purification of staphylococcal 

enterotoxin B. Biochemistry 4(6): 1011– 

6. 

14. Wang, S., Y. Li, et al., 2008. A broadspectrum inhibitory peptide against 

staphylococcal enterotoxin superantigen 

SEA, SEB and SEC. Immunol Lett 121(2): 

167–72. 

15. Munson, S.H., M.T. Tremaine, et al., 

1998. Identification and characterization 

of staphylococcal enterotoxin types G 

and I from Staphylococcus aureus. Infect 

Immun 66(7): 3337–48. 

16. H.Su, Y.C. and A.C. Wong, 1995. 

Identification and purification of a new 

staphylococcal enterotoxin. Appl 

Environ Microbiol 61(4): 1438–43. 

17. Zhang, S., J.J. Iandolo, et al., 1998.The 

enterotoxin D plasmid of Staphylococcus 

aureus encodes a second enterotoxin 

determinant (sej). FEMS Microbiol Lett 

168(2): 227–33. 

18. Orwin, P.M., J.R. Fitzgerald, et al., 2003. 

Characterization of Staphylococcus 

aureus enterotoxin L. Infect Immun 

71(5): 2916–9. 

19. Orwin, P.M., D.Y. Leung, et al., 2001. 

Biochemical and biological properties of 

Staphylococcal enterotoxin K. Infect 

Immun 69(1): 360–6. 

20. Orwin, P.M., D.Y. Leung, et al., 2002. 

Characterization of a novel 

staphylococcal enterotoxin-like 

superantigen, a member of the group V 

subfamily of pyrogenic toxins. 

Biochemistry 41(47): 14033–40. 

21. Jarraud, S., M.A. Peyrat, et al., 2001. Egc, 

a highly prevalent operon of enterotoxin 

gene, forms a putative nursery of 

superantigens in Staphylococcus aureus. 

J Immunol 166(1): 669–77. 

22. Kuroda, M., T. Ohta, et al., 2001. Whole 

genome sequencing of meticillinresistant Staphylococcus aureus. Lancet 

357(9264): 1225–40. 

23. Omoe, K., K. Imanishi, et al., 2004. 

Biological properties of staphylococcal 

enterotoxin-like toxin type R. Infect 

Immun 72(6): 3664–7. 

24. Ono, H.K., K. Omoe, et al., 2008. 

Identification and characterization of 

two novel staphylococcal enterotoxins, 

types S and T. Infect Immun 76(11): 

4999–5005. 


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Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 61221 

25. Letertre, C., S. Perelle, et al., 2003. 

Identification of a new putative 

enterotoxin SEU encoded by the egc 

cluster of Staphylococcus aureus. J Appl 

Microbiol 95(1): 38–43. 

26. Thomas, D.Y., S. Jarraud, et al., 2006. 

Staphylococcal enterotoxin-like toxins 

U2 and V, two new staphylococcal 

superantigens arising from 

recombination within the enterotoxin 

gene cluster. Infect Immun 74(8): 4724– 

34. 

27. Medina RA, Manicassamy B, Stertz S, 

Seibert CW, Hai R, Belshe RB, Frey SE, 

Basler CF, Palese P, Garcı ́a-Sastre A. 

Pandemic 2009 H1N1 vaccine protects 

against 1918 Spanish influenza virus. 

Nat Commun. 2010 Jun 15;1:28. doi: 

10.1038/ncomms1026. 

28. Tumpey TM, Garcı ́a-Sastre A, Mikulasova 

A, Taubenberger JK, Swayne DE, Palese 

P, Basler CF. Existing antivirals are 

effective against influenza viruses with 

genes from the 1918 pandemic virus. 

Proc Natl Acad Sci U S A. 2002 Oct 

15;99(21):13849–54. Epub 2002 Oct 4. 

29. Xiao Y, Isaacs SN. Therapeutic Vaccines 

and Antibodies for Treatment of 

Orthopoxvirus Infections. Viruses. 2010 

Oct;2(10):2381–2403. 

30. Rimoin AW, Mulembakani PM, Johnston 

SC, Lloyd Smith JO, Kisalu NK, Kinkela 

TL, Blumberg S, Thomassen HA, Pike 

BL, Fair JN, Wolfe ND, Shongo RL, 

Graham BS, Formenty P, Okitolonda E, 

Hensley LE, Meyer H, Wright LL, 

Muyembe JJ. Major increase in human 

monkeypox incidence 30 years after 

smallpox vaccination campaigns cease in 

the Democratic Republic of Congo. Proc 

Natl Acad Sci U S A. 2010 Sep 

14;107(37):16262–7. Epub 2010 Aug 30. 

31. Reynolds MG, Carroll DS, Olson VA, 

Hughes C, Galley J, Likos A, Montgomery 

JM, Suu-Ire R, Kwasi MO, Jeffrey Root J, 

Braden Z, Abel J, Clemmons C, Regnery 

R, Karem K, Damon IK. A silent enzootic 

of an orthopoxvirus in Ghana, West 

Africa: evidence for multi-species 

involvement in the absence of 

widespread human disease. Am J Trop 

Med Hyg. 2010 Apr;82(4):746–54. 

32. Di Giulio DB, Eckburg PB. Human 

monkeypox: an emerging zoonosis. 

Lancet Infect Dis. 2004 Jan;4(1):15–25. 

33. Hutson CL, Lee KN, Abel J, Carroll DS, 

Montgomery JM, Olson VA, Li Y, 

Davidson W, Hughes C, Dillon M, 

Spurlock P, Kazmierczak JJ, Austin C, 

Miser L, Sorhage FE, Howell J, Davis JP, 

Reynolds MG, Braden Z, Karem KL, 

Damon IK, Regnery RL. Monkeypox 

zoonotic associations: insights from 

laboratory evaluation of animals 

associated with the multi-state US 

outbreak. Am J Trop Med Hyg. 2007 

Apr;76(4):757–68. 

List of Subjects in 42 CFR Part 73 

Biologics, Incorporation by reference, 

Packaging and containers, Penalties, 

Reporting and recordkeeping 

requirements, Transportation. 

For the reasons stated in the 

preamble, the Centers for Disease 

Control and Prevention, United States 

Department of Health and Human 

Services, proposes to amend 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 

107–188, 116 Stat 637 (42 U.S.C. 262a). 

2. Section 73.1 is amended by adding, 

in alphabetical order, definitions of 

Adjudicated as a mental defective, 

Alien, Committed to any mental 

institution, Controlled substance, Crime 

punishable by imprisonment for a term 

exceeding 1 year, Indictment, 

Information security, Lawfully admitted 

for permanent residence, Mental 

institution, Occupational exposure, 

Recombinant and synthetic nucleic 

acids, Restricted person, and Unlawful 

user of any controlled substance to read 

as set forth below. 

§ 73.1 Definitions. 

* * * * * 

Adjudicated as a mental defective. A 

determination by a court, board, 

commission, or other lawful authority 

that a person, as a result of marked 

subnormal intelligence, or mental 

illness, incompetency, condition, or 

disease is a danger to himself/herself or 

to others or lacks the mental capacity to 

contract or manage his/her own affairs. 

The term includes a finding of insanity 

by a court in a criminal case and those 

persons found incompetent to stand 

trial or found not guilty by reason of 

lack of mental responsibility pursuant to 

articles 50a and 72b of the Uniform 

Code of Military Justice, 10 U.S.C. 850a, 

876b. 

Alien. Any person not a citizen or 

national of the United States. 

* * * * * 

Committed to any mental institution. 

A formal commitment of a person to any 

mental institution by a court, board, 

commission, or other lawful authority. 

The term includes a commitment to a 

mental institution involuntarily. The 

term includes commitment for mental 

defectiveness or mental illness. It also 

includes commitments for other 

reasons, such as for drug use. The term 

does not include a person in a mental 

institution for observation or a 

voluntary admission to a mental 

institution. 

Controlled substance. A drug or other 

substance, or immediate precursor, as 

defined in section 102 of the Controlled 

Substances Act, 21 U.S.C. 802. The term 

includes, but is not limited to, 

marijuana and scheduled depressants, 

stimulants, and narcotic drugs. The term 

does not include distilled spirits, wine, 

malt beverages, or tobacco, as those 

terms are defined or used in Subtitle E 

of the Internal Revenue Code of 1986, as 

amended. 

Crime punishable by imprisonment 

for a term exceeding 1 year. Any 

Federal, State, or foreign offense for 

which the maximum penalty, whether 

or not imposed, is capital punishment 

or imprisonment in excess of 1 year. 

What constitutes a conviction of such a 

crime shall be determined in accordance 

with the law of the jurisdiction in which 

the proceedings were held. Any 

conviction that has been set aside or 

nullified as a matter of law or for which 

a person has been pardoned shall not be 

considered a conviction for purposes of 

this part. 

* * * * * 

Indictment. A formal written 

accusation originating with a prosecutor 

and issued by a grand jury against a 

party charged with a crime. For the 

purpose of these regulations the term 

indictment includes any ‘‘information’’ 

that is a formal accusation of a crime, 

differing only in that it is being 

presented by a competent public officer 

on his oath of office, instead of a grand 

jury. 

Information security. Protecting 

information and information systems 

from unauthorized access, use, 

disclosure, disruption, modification, or 

destruction in order to provide— 

(1) Integrity, which means guarding 

against improper information 

modification or destruction, and 

includes ensuring information 

nonrepudiation and authenticity; 

(2) Confidentiality, which means 

preserving authorized restrictions on 

access and disclosure, including means 

for protecting personal privacy and 

proprietary information; and 

(3) Availability, which means 

ensuring timely and reliable access to 

and use of information. 

* * * * * 

Lawfully admitted for permanent 

residence. The status of having been 

lawfully accorded the privilege of 

residing permanently in the United 

States as an immigrant in accordance 

with the immigration laws, such status 

not having changed. 

Mental institution. Includes mental 

health facilities, mental hospitals, 

sanitariums, psychiatric facilities, and 

other facilities that provide diagnoses by 

licensed professionals of mental 

retardation or mental illness, including 

a psychiatric ward in a general hospital. 

* * * * * 


srobinson on DSK4SPTVN1PROD with PROPOSALS2
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1 Including all toxin derivatives, both naturally 

occurring and synthetic, that retain function. 

Occupational exposure. Any 

reasonably anticipated skin, eye, 

mucous membrane, or parenteral 

contact with blood or other potentially 

infectious materials or toxins that may 

result from the performance of an 

employee’s duties. 

* * * * * 

Recombinant and synthetic nucleic 

acids. 

(1) Recombinant nucleic acid 

molecules that are constructed by 

joining nucleic acid molecules and that 

can replicate in a living cell; 

(2) Synthetic nucleic acid molecules 

that are chemically, or by other means, 

synthesized or amplified nucleic acid 

molecules that may wholly or partially 

contain functional equivalents of 

nucleotides; or 

(3) Molecules that result from the 

replication of those described in 

paragraphs (1) or (2) of this definition. 

* * * * * 

Restricted person. An individual who: 

(1) Is under indictment for a crime 

punishable by imprisonment for a term 

exceeding 1 year; 

(2) Has been convicted in any court of 

a crime punishable by imprisonment for 

a term exceeding 1 year; 

(3) Is a fugitive from justice; 

(4) Is an unlawful user of any 

controlled substance (as ‘‘controlled 

substance’’ is defined in section 102 of 

the Controlled Substances Act (21 

U.S.C. 802)); 

(5) Is an alien illegally or unlawfully 

in the United States; 

(6) Has been adjudicated as a mental 

defective or has been committed to any 

mental institution; 

(7) Is an alien (other than an alien 

lawfully admitted for permanent 

residence) who is a national of a country 

as to which the Secretary of State, 

pursuant to section 6(j) of the Export 

Administration Act of 1979 (50 U.S.C. 

App. 2405(j)), section 620A of chapter 1 

of part M of the Foreign Assistance Act 

of 1961 (22 U.S.C. 2371), or section 

40(d) of chapter 3 of the Arms Export 

Control Act (22 U.S.C. 2780d), has made 

a determination (that remains in effect) 

that such country has repeatedly 

provided support for acts of 

international terrorism; or 

(8) Has been discharged from the 

Armed Services of the United States 

under dishonorable conditions. 

* * * * * 

Unlawful user of any controlled 

substance. For purposes of this part, a 

person who uses a controlled substance 

and has lost the power of self-control 

with reference to the use of that 

controlled substance; and any person 

who is a current user of a controlled 

substance in a manner other than as 

prescribed by a licensed physician. 

Such use is not limited to the use of 

drugs on a particular day, or within a 

matter of days or weeks before, but 

rather that the unlawful use has 

occurred recently enough to indicate 

that the individual is actively engaged 

in such conduct. A person may be an 

unlawful current user of a controlled 

substance even though the substance is 

not being used at the precise time the 

person seeks to have access to a select 

agent or toxin. An inference of current 

use may be drawn from evidence of a 

recent use or possession of a controlled 

substance or a pattern of use or 

possession that reasonably covers the 

present time, e.g., a conviction for use 

or possession of a controlled substance 

within the past year; multiple arrests for 

such offenses within the past 5 years if 

the most recent arrest occurred within 

the past year, or persons found through 

a drug test to use a controlled substance 

unlawfully, provided that the test was 

administered within the past year. For 

a current or former member of the 

Armed Forces, an inference of current 

use may be drawn from recent 

disciplinary or other administrative 

action based on confirmed drug use, 

e.g., court-martial conviction, 

nonjudicial punishment, or an 

administrative discharge based on drug 

use or drug rehabilitation failure. 

* * * * * 

3. Section 73.3 is amended as follows: 

a. By adding a sentence to the end of 

paragraph (a) to read as set forth below. 

b. By revising paragraph (b) to read as 

set forth below. 

c. In paragraph (c), in the introductory 

text, by adding the phrase ‘‘and/or 

Synthetic’’ after the word 

‘‘Recombinant’’ each time it appears. 

d. In paragraph (c)(2) introductory 

text, by adding the phrase ‘‘and/or 

synthetic’’ after the word 

‘‘Recombinant’’. 

e. By revising paragraph (d)(3) to read 

as set forth below. 

f. By adding a new paragraph (d)(4) to 

read as set forth below. 

g. By revising paragraph (e) to read as 

set forth below. 

h. In paragraph (f)(3)(i), by removing 

the words ‘‘Lassa fever virus, South 

American Haemorrhagic Fever virus 

(Junin, Machupo, Sabia, Flexal, 

Guanarito)’’ and by adding the words 

‘‘Botulinum neurotoxin producing 

species of Clostridium.’’ 

§ 73.3 HHS select agents and toxins. 

(a) * * * The select agents and toxins 

marked with an asterisk (*) are 

designated as Tier 1 select agents and 

toxins and are subject to additional 

requirements as listed in this part. 

(b) HHS select agents and toxins: 1

Abrin 

Botulinum neurotoxins* 

Botulinum neurotoxin producing 

species of Clostridium* 

Chapare 

Clostridium perfringens epsilon toxin 

Conotoxins 

Coxiella burnetii 

Crimean-Congo haemorrhagic fever 

virus 

Diacetoxyscirpenol 

Eastern Equine Encephalitis virus 

(North American genotypes) 

Ebola virus* 

Francisella tularensis* 

Lassa fever virus 

Lujo 

Marburg virus* 

Monkeypox virus 

Reconstructed replication competent 

forms of the 1918 pandemic influenza 

virus containing any portion of the 

coding regions of all eight gene 

segments (Reconstructed 1918 Influenza 

virus) 

Ricin 

Rickettsia prowazekii 

Rickettsia rickettsii 

Saxitoxin 

Shiga-like ribosome inactivating 

proteins 

Shigatoxin 

South American Haemorrhagic Fever 

viruses 

Guanarito 

Junin 

Machupo 

Sabia 

Staphylococcal enterotoxins (SE) A–E 

(SEA, SEB, SEC, SED, SEE) 

T–2 toxin 

Tetrodotoxin 

Tick-borne encephalitis virus 

Far Eastern subtype 

Siberian subtype 

Kyasanur Forest disease virus 

Omsk hemorrhagic fever virus 

Variola major virus (Smallpox virus)* 

Variola minor virus (Alastrim)* 

Yersinia pestis* 

* * * * * 

(d) * * * 

(3) Except as required in § 73.16(l), 

HHS toxins under the control of a 

principal investigator, treating 

physician or veterinarian, or 

commercial manufacturer or distributor, 

if: 

(i) The aggregate amount does not, at 

any time, exceed the following amounts: 

100 mg of Abrin; 0.5 mg of Botulinum 

neurotoxins; 100 mg of Clostridium 


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perfringens epsilon toxin; 100 mg of 

Conotoxins; 1,000 mg of 

Diacetoxyscirpenol; 100 mg of Ricin; 

100 mg of Saxitoxin; 100 mg of Shigalike ribosome inactivating proteins; 100 

mg of Shigatoxin; 5 mg of 

Staphylococcal enterotoxins; 1,000 mg 

of T–2 toxin; or 100 mg of Tetrodotoxin. 

(ii) Amounts of toxins equal to or less 

than the amounts identified in 

paragraph (d)(3)(i) of this section are 

transferred only after the transferor uses 

due diligence and documents that the 

recipient has a legitimate need (i.e. 

reasonably justified by a prophylactic, 

protective, bona fide research, or other 

peaceful purpose) to handle or use such 

toxins. Notwithstanding the provisions 

of paragraph (d) of this section, the HHS 

Secretary retains the authority to, 

without prior notification, inspect and 

copy or request the submission of the 

due diligence documentation to the 

CDC. 

(iii) The transfer of amounts of toxins 

equal to or less than the amounts 

identified in paragraph (d)(3)(i) of this 

section reports to CDC if they detect a 

known or suspected violation of Federal 

law or become aware of suspicious 

activity related to a toxin listed in 

section of this part. 

(4) Notwithstanding paragraph 

(d)(3)(i) of this section, an animal 

inoculated with or exposed to an HHS 

select toxin. 

(e) An attenuated strain of a select 

agent or an inactive form of a select 

toxin may be excluded from the 

requirements of this part based upon a 

determination by the HHS Secretary that 

the attenuated strain or inactivated 

toxin does not pose a severe threat to 

public health and safety. 

(1) To apply for exclusion, an 

individual or entity must submit a 

written request and supporting 

scientific information. A written 

decision granting or denying the request 

will be issued. An exclusion will be 

effective upon notification to the 

applicant. Exclusions will be listed on 

the National Select Agent Registry Web 

site at http://www.selectagents.gov/. 

(2) If an excluded attenuated strain or 

inactivated toxin is subjected to any 

manipulation that restores or enhances 

its virulence or toxic activity, the 

resulting select agent or toxin will be 

subject to the requirements of this part. 

* * * * * 

4. Section 73.4 is amended as follows: 

a. By adding a sentence to the end of 

paragraph (a) to read as set forth below. 

b. By revising paragraph (b) to read as 

set forth below. 

c. In paragraph (c), in the introductory 

text, by adding the phrase ‘‘and/or 

synthetic’’ after the word 

‘‘Recombinant’’ each time it appears. 

d. In paragraph (c)(2), by adding the 

phrase ‘‘and/or synthetic’’ after the 

word ‘‘Recombinant’’. 

e. By revising paragraph (e) to read as 

set forth below. 

f. In paragraph (f)(3)(i), by removing 

the words ‘‘Brucella melitensis, Hendra 

virus, Nipah virus, Rift Valley fever 

virus, and Venezuelan equine 

encephalitis virus’’ and adding the 

words ‘‘Burkholderia mallei and 

Burkholderia pseudomallei’’ in their 

place. 

§ 73.4 Overlap select agents and toxins. 

(a) * * * The select agents and toxins 

marked with an asterisk (*) are 

designated as Tier 1 select agents and 

toxins and are subject to additional 

requirements as listed in this part. 

(b) Overlap select agents and toxins: 

Bacillus anthracis;* 

Brucella abortus; 

Brucella melitensis; 

Brucella suis; 

Burkholderia mallei;* 

Burkholderia pseudomallei;* 

Hendra virus; 

Nipah virus; 

Rift Valley fever virus; 

Venezuelan equine encephalitis virus: 

Epizootic Subtypes IAB, IC. 

* * * * * 

(e) An attenuated strain of a select 

agent or an inactive form of a select 

toxin may be excluded from the 

requirements of this part based upon a 

determination by the HHS Secretary or 

Administrator that the attenuated strain 

or inactivated toxin does not pose a 

severe threat to public health and safety, 

to animal health or to animal products. 

(1) To apply for exclusion, an 

individual or entity must submit a 

written request and supporting 

scientific information. A written 

decision granting or denying the request 

will be issued. An exclusion will be 

effective upon notification to the 

applicant. Exclusions will be listed on 

the National Select Agent Registry Web 

site at http://www.selectagents.gov/. 

(2) If an excluded attenuated strain or 

inactivated toxin is subjected to any 

manipulation that restores or enhances 

its virulence or toxic activity, the 

resulting select agent or toxin will be 

subject to the requirements of this part. 

* * * * * 

§ 73.5 [Amended] 

5. Section 73.5(a)(3)(i) is amended by 

removing the words ‘‘Lassa fever virus, 

South American Haemorrhagic Fever 

virus (Junin, Machupo, Sabia, Flexal, 

Guanarito)’’ and by adding the words 

‘‘Botulinum neurotoxin producing 

species of Clostridium’’ in their place. 

§ 73.6 [Amended] 

6. Section 73.6(a)(3)(i) is amended by 

removing the words ‘‘Brucella 

melitensis, Hendra virus, Nipah virus, 

Rift Valley fever virus, and Venezuelan 

equine encephalitis virus’’ and adding 

the words ‘‘Burkholderia mallei and 

Burkholderia pseudomallei’’ in their 

place. 

§ 73.8 [Amended] 

7. Section 73.8 (a)(1) is amended by 

removing the words ‘‘within any of the 

categories described in 18 U.S.C. 175b’’ 

and adding the words ‘‘a restricted 

person’’ in their place. 

* * * * * 

8. Section 73.9 is amended as follows: 

a. By redesignating paragraphs (a)(3) 

through (a)(5) as paragraphs (a)(4) 

through (a)(6) respectively. 

b. By adding a new paragraph (a)(3) to 

read as set forth below. 

c. In newly redesignated paragraph 

(a)(5), by removing the word ‘‘and’’. 

d. By further redesignating newly 

redesignated paragraph (a)(6) as 

paragraph (a)(7). 

e. By adding a new paragraph (a)(6) to 

read as set forth below. 

f. By revising the first sentence of 

paragraph (b) to read as set forth below. 

g. In paragraph (c)(1), by removing the 

words ‘‘Bacillus anthracis, Botulinum 

neurotoxins, Brucella melitensis, 

Francisella tularensis, Ebola viruses, 

Hendra virus, Marburg virus, Lassa fever 

virus, Nipah virus, Rift Valley fever 

virus, South American Haemorrhagic 

Fever viruses (Junin, Machupo, Sabia, 

Flexal, Guanarito), Variola major virus 

(Smallpox virus), Variola minor 

(Alastrim), Venezuelan equine 

encephalitis virus and Yersina pestis’’ 

and adding the words ‘‘Bacillus 

anthracis, Botulinum neurotoxins, 

Botulinum neurotoxin producing 

species of Clostridium, Burkholderia 

mallei, Burkholderia pseudomallei, 

Francisella tularensis, Ebola viruses, 

Marburg virus, Variola major virus 

(Smallpox virus), Variola minor 

(Alastrim), and Yersinia pestis’’ in their 

place. 

(a) * * * 

(3) Have the appropriate training and 

expertise to competently implement and 

manage the requirements of this part; 

* * * * * 

(6) Have their principal duty station at 

the physical location of the entity; and 

* * * * * 

(b) An entity may designate one or 

more individuals to serve as an alternate 

Responsible Official, who acts for the 

Responsible Official in his/her absence. 

* * * 

* * * * * 


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9. Section 73.10 is amended as 

follows: 

a. By redesignating paragraphs (e) 

through (j) as paragraphs (f) through (k) 

respectively. 

b. By adding a new paragraph (e) to 

read as set forth below. 

c. In newly redesignated paragraph 

(g), by removing the words ‘‘within any 

of the categories described in 18 U.S.C. 

175b’’ and adding the words ‘‘a 

restricted person’’ in their place. 

d. In newly redesignated paragraph 

(j), by removing the word ‘‘five’’ and 

adding the word ‘‘three’’ in its place. 

§ 73.10 Restricting access to select agents 

and toxins; security risk assessments. 

* * * * * 

(e) A person who has a valid approval 

from the HHS Secretary or 

Administrator for access to a select 

agent or toxin may request the HHS 

Secretary or Administrator to provide 

the person’s approval status to another 

registered individual or entity for a 

specified period of time. 

* * * * * 

10. Section 73.11 is amended as 

follows: 

a. By revising paragraph (b) to read as 

set forth below. 

b. By revising paragraph (c)(2) to read 

as set forth below. 

c. By adding new paragraphs (c)(8), 

(c)(9), and (c)(10) to read as set forth 

below. 

d. By redesignating paragraphs (e) and 

(f) as paragraphs (f) and (g), respectively 

and by revising redesignated paragraph 

(f) to read as set forth below. 

e. By adding a new paragraph (e) to 

read as set forth below. 

§ 73.11 Security. 

* * * * * 

(b) The security plan must be 

designed according to a site-specific risk 

assessment and must provide graded 

protection in accordance with the risk of 

the select agent or toxin, given its 

intended use. A current security plan 

must be submitted for initial 

registration, renewal of registration, or 

when requested. 

(c) * * * 

(2) Contain provisions for the control 

of access to select agents and toxins, 

including the safeguarding of animals or 

plants intentionally or accidentally 

exposed to or infected with a select 

agent, against unauthorized access, 

theft, loss or release. 

* * * * * 

(8) Describe procedures for how the 

Responsible Official will be informed of 

suspicious activity that may be criminal 

in nature and related to the entity, its 

personnel, or its select agents or toxins; 

and how the Responsible Official will 

notify the Federal Bureau of 

Investigation (FBI) of such activity, 

(9) Contain provisions for information 

security that: 

(i) Ensure that all external 

connections to systems which control 

security of the facility are isolated or 

have controls that permit and monitor 

for only authorized and authenticated 

user access; 

(ii) Ensure that authorized and 

authenticated users are only granted 

access to select agent and toxin related 

information, files, equipment (e.g., 

servers or mass storage devices) and 

applications as necessary to fulfill their 

roles and responsibilities, and that 

access is modified when the user’s roles 

and responsibilities change or when 

their access to select agent and toxin is 

suspended or revoked; 

(iii) Ensure that controls are in place 

that are designed to prevent malicious 

code (such as, but not limited to, 

computer virus, worms, spyware) from 

compromising the confidentiality, 

integrity, or availability of information 

systems; 

(iv) Establish a robust configuration 

management practice for information 

systems to include regular patching and 

updates made to operating systems and 

individual applications; and 

(v) Establish procedures that provide 

backup security measures in the event 

that access control systems and/or 

surveillance devices are rendered 

inoperable. 

(10) Contain provisions and policies 

for shipping, receiving, and storage of 

select agents and toxins, including 

documented procedures for receiving, 

monitoring, and shipping of all select 

agents and toxins. These provisions 

must provide that an entity will 

properly secure containers on site and 

have a written contingency plan for 

unexpected shipments. 

* * * * * 

(e) In addition to the requirements 

contained in paragraphs (c) and (d) of 

this section, the security plan for an 

individual or entity possessing a Tier 1 

select agent or toxin must also: 

(1) Describe procedures for 

conducting a pre-access suitability 

assessment of persons who will have 

access to a Tier 1 select agent or toxin; 

(2) Describe procedures for how an 

entity’s Responsible Official will 

coordinate their efforts with the entity’s 

safety and security professionals to 

ensure security of Tier 1 select agents 

and toxins and share, as appropriate, 

relevant information; and 

(3) Describe procedures for the 

ongoing assessment of the suitability of 

personnel with access to a Tier 1 select 

agent or toxin. The procedures must 

include: 

(i) Self- and peer-reporting of 

incidents or conditions that could affect 

an individual’s ability to safely have 

access to or work with select agents and 

toxins, or to safeguard select agents and 

toxins from theft, loss, or release; 

(ii) The training of all entity 

employees on entity policies and 

procedures for reporting, evaluation, 

and corrective actions concerning the 

assessment of personnel suitability to 

access Tier 1 agents and toxins; and 

(iii) The ongoing suitability 

monitoring of individuals with access to 

Tier 1 select agents and toxins. 

(4) Entities with Tier 1 select agents 

and toxins must prescribe and/or 

implement the following security 

enhancements: 

(i) Procedures that will limit access to 

registered space only to those approved 

by the HHS Secretary or the 

Administrator and meet the criteria of 

the entity’s program that will ensure 

individuals with access approval to 

select agents and toxins are trustworthy 

and behaving in a manner that upholds 

public health and safety, security, and 

the integrity of the scientific enterprise. 

(ii) Procedures that limit access to 

laboratory and storage facilities outside 

of normal business hours to only those 

specifically approved by the 

Responsible Official or designee; 

(iii) Procedures for allowing visitors, 

their property, and vehicles at the entry 

and exit points to the registered space, 

or at other designated points of entry to 

the building, facility, or compound 

based on the entity’s site-specific risk 

assessment; 

(iv) A minimum of three barriers 

where each subsequent barrier is 

different and adds to the delay in 

reaching secured areas where select 

agents and toxins are used or stored. 

Barriers must be monitored in such a 

way as to detect and assess intentional 

and unintentional circumventing of 

established access control measures 

under all conditions (day/night, severe 

weather, etc.); 

(v) All registered space or areas that 

reasonably afford access to the 

registered space must be protected by an 

intrusion detection system (IDS) unless 

physically occupied; 

(vi) Personnel monitoring the IDS 

must be capable of evaluating and 

interpreting the alarm and alerting the 

designated security response force or 

law enforcement; 

(vii) Provide backup power and 

energy sources to power information 

security networks and integrated access 


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2Nothing in this section is meant to supersede or 

preempt incident response requirements imposed 

by other statutes or regulations. 

controls and related systems during 

emergencies; 

(viii) Response time for security forces 

or local police must not exceed 15 

minutes from the time of an intrusion 

alarm or report of a security incident; 

(ix) Entities must conduct complete 

inventory audits of all Tier 1 select 

agents and toxins in long-term storage 

when any of the following occur: 

(A) Upon the physical relocation of a 

collection or inventory of select agents 

or toxins for those Tier 1 select agents 

or toxins in the collection or inventory; 

(B) Upon the departure or arrival of a 

principal investigator for those Tier 1 

select agents and toxins under the 

control of that principal investigator; or 

(C) In the event of a theft or loss of 

a Tier 1 select agent or toxin. 

(5) Entities that possess Variola major 

virus and Variola minor virus must have 

the following additional security 

requirements: 

(i) Require personnel with access to 

Variola major or Variola minor virus to 

have a Top Secret security clearance, 

(ii) Require Variola major or Variola 

minor virus storage locations be under 

the surveillance of closed circuit 

television that is monitored, 

(iii) After hours access procedures for 

Variola major or Variola minor virus 

must require notification of the entity’s 

security staff prior to entry into the 

Variola laboratory and upon exit, 

(iv) Require that observation zones be 

maintained in outdoor areas adjacent to 

the physical barrier at the perimeter of 

the entity and be large enough to permit 

observation of the activities of people at 

that barrier in the event of its 

penetration, 

(v) Provide for a minimum of four 

barriers for the protection of the Variola 

major or Variola minor virus, one of 

which must be a perimeter fence, 

(vi) Require a numbered picture badge 

identification subsystem to be used for 

all individuals who are authorized to 

access Variola major or Variola minor 

without escort, 

(vii) Require the use, at all times, of 

properly trained, and equipped security 

force personnel able to interdict threats 

identified in the site specific risk 

assessment, 

(viii) Identify security force personnel 

designated to strengthen onsite response 

capabilities, and that will be onsite and 

available at all times to carry out their 

assigned response duties, 

(ix) Provide for security patrols to 

periodically check external areas of the 

registered areas to include physical 

barriers and building entrances, 

(x) Require that all on-duty security 

force personnel shall be capable of 

maintaining continuous communication 

with support and response assets by 

way of security operations center, 

(xi) Require that Variola major and 

Variola minor material in long term 

storage be stored in tamper-indicating 

containers, 

(xii) Require that all spaces containing 

working or permanent Variola major or 

Variola minor stocks be locked and 

protected by an intrusion alarm system 

that will alarm upon the unauthorized 

entry of a person anywhere into the 

area, 

(xiii) Require that alarms required 

pursuant to this section annunciate in a 

continuously manned security 

operations center located within the 

facility, 

(xiv) Require that the security 

operations center shall be located 

within a building so that the interior is 

not visible from the perimeter of the 

protected area. 

(f) In developing a security plan, an 

individual or entity should consider the 

documents entitled, ‘‘Select Agents and 

Toxins Security Information Document’’ 

and ‘‘Select Agents and Toxins Security 

Plan Template.’’ These documents are 

available on the Internet at http:// 

www.selectagents.gov/. 

* * * * * 

11. Section 73.12 is amended as 

follows: 

a. By revising paragraph (a) to read as 

set forth below. 

b. By revising paragraph (c)(1) to read 

as set forth below. 

c. In paragraph (c)(3), by removing the 

URL ‘‘http://www.cdc.gov/’’ and adding 

in its place ‘‘http:// 

www.selectagents.gov’’. 

d. By redesignating paragraph (d) as 

paragraph (e). 

e. By adding a new paragraph (d) to 

read as set forth below. 

§ 73.12 Biosafety. 

* * * * * 

(a) An individual or entity required to 

register under this part must develop 

and implement a written biosafety plan 

that is commensurate with the risk of 

the select agent or toxin, given its 

intended use. The biosafety plan must 

contain sufficient information and 

documentation to describe the biosafety 

and containment procedures for the 

select agent or toxin, including any 

animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent. 

* * * * * 

(c) * * * 

(1) The CDC/NIH publication, 

‘‘Biosafety in Microbiological and 

Biomedical Laboratories.’’ This 

document is available on the Internet at 

http://www.selectagents.gov. 

* * * * * 

(d) The biosafety plan must include 

an occupational health program for 

individuals with access to Tier 1 select 

agents and toxins, and those individuals 

must be enrolled in the occupational 

health program. The occupational 

health program may also be made 

available to individuals without access 

to Tier 1 select agents and toxins. 

* * * * * 

§ 73.13 [Amended] 

12. Section 73.13 is amended as 

follows: 

a. In paragraph (a), in the introductory 

text, by adding the phrase ‘‘, or possess 

products (i.e. select agents that are not 

known to acquire the resistance 

naturally, if such acquisition could 

compromise the use of the drug to 

control disease agents in humans, 

veterinary medicine, or agriculture, or 

recombinant and or synthetic DNA 

containing genes for the biosynthesis of 

select toxins lethal for vertebrates at an 

LD[50] < 100 ng/kg body weight) 

resulting from,’’ after the word 

‘‘conduct’’ both times it appears. 

b. In paragraph (b)(1), by removing the 

words ‘‘Experiments utilizing 

recombinant DNA that involve the 

deliberate transfer of’’ and replacing 

them with the words ‘‘Experiments that 

involve the deliberate transfer of, or 

selection for,’’. 

c. In paragraph (b)(2), by adding the 

words ‘‘synthetic or’’ before the word 

‘‘recombinant.’’ 

13. Section 73.14 is amended as 

follows: 

a. By revising paragraph (a) to read as 

set forth below. 

b. By revising paragraph (b) to read as 

set forth below. 

c. By redesignating paragraph (c) and 

(d) as paragraphs (d) and (f) 

respectively. 

d. By adding a new paragraph (c) to 

read as set forth below. 

e. By adding a new paragraph (e) to 

read as set forth below. 

§ 73.14 Incident response. 

(a) An individual or entity required to 

register under this part must develop 

and implement a written incident 

response plan based upon a site specific 

risk assessment.2 The incident response 

plan must be coordinated with any 

entity-wide plans, kept in the 


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61226 Federal Register / Vol. 76, No. 191 / Monday, October 3, 2011 / Proposed Rules 

workplace, and available to employees 

for review. 

(b) The incident response plan must 

fully describe the entity’s response 

procedures for the theft, loss, or release 

of a select agent or toxin; inventory 

discrepancies; security breaches 

(including information systems); severe 

weather and other natural disasters; 

workplace violence; bomb threats and 

suspicious packages; and emergencies 

such as fire, gas leak, explosion, power 

outage, etc. 

(c) The response procedures must 

account for hazards associated with the 

select agent or toxin and appropriate 

actions to contain such select agent or 

toxin, including any animals or plants 

intentionally or accidentally exposed to 

or infected with a select agent. 

* * * * * 

(e) Entities with Tier 1 select agents 

and toxins must have the following 

additional incident response policies or 

procedures: 

(1) The incident response plan must 

fully describe the entity’s response 

procedures for failure of intrusion 

detection or alarm system; and 

(2) The incident response plan must 

describe notification procedures for the 

FBI in the event of a theft or suspicious 

activity that may be criminal in nature 

involving a Tier 1 select agent or toxin. 

* * * * * 

14. Section 73.15 is revised to read as 

follows: 

§ 73.15 Training. 

(a) An individual or entity required to 

register under this part must provide 

information and training on biosafety, 

security (including security awareness) 

and incident response: 

(1) To each individual with access 

approval from the HHS Secretary or 

Administrator before that individual has 

such access to select agents and toxins. 

The training must address the particular 

needs of the individual, the work they 

will do, and the risks posed by the 

select agents or toxins. 

(2) To each individual not approved 

for access to select agents and toxins by 

the HHS Secretary or Administrator 

before that individual enters areas 

where select agents or toxins are 

handled or stored (e.g., laboratories, 

growth chambers, animal rooms, 

greenhouses, storage areas, shipping/ 

receiving areas, production facilities, 

etc.). Training for escorted personnel 

must be based on the risk associated 

with accessing areas where select agents 

and toxins are used and/or stored. 

(b) Entities with Tier 1 select agents 

and toxins must conduct annual insider 

threat awareness briefings on how to 

identify and report suspicious 

behaviors. 

(c) Refresher training must be 

provided annually or at such time as the 

registered individual or entity 

significantly amends its security, 

incident response, or biosafety plans. 

(d) The Responsible Official must 

ensure a record of the training provided 

to each individual with access to select 

agents and each escorted individual 

(e.g., laboratory workers, visitors, etc.) is 

maintained. The record must include 

the name of the individual, the date of 

the training, a description of the training 

provided, and the means used to verify 

that the employee understood the 

training. 

15. Section 73.16 is amended as 

follows: 

a. By redesignating paragraph (f), (g), 

(h), and (i) as paragraphs (i), (j), (k), and 

(g) respectively. 

b. In redesignated paragraph (g), by 

removing the words ‘‘packaging and’’. 

c. By adding a new paragraph (f) to 

read as set forth below. 

d. By adding a new paragraph (h) to 

read as set forth below. 

e. By adding a new paragraph (l) to 

read as set forth below. 

§ 73.16 Transfers. 

* * * * * 

(f) After authorization is provided by 

APHIS or CDC, the select agent(s) and 

toxin(s) are packaged for shipment in 

compliance with all applicable laws 

concerning packaging by an individual 

approved by the HHS Secretary or 

Administrator to have access to select 

agents and toxins, following a security 

risk assessment by the Attorney General. 

* * * * * 

(h) Transportation in commerce starts 

when the select agent(s) or toxin(s) are 

packaged for shipment and ready for 

receipt by a courier transporting select 

agent(s) or toxin(s) and ends when the 

package is received by the intended 

recipient who is an individual approved 

by the HHS Secretary or Administrator 

to have access to select agents and 

toxins, following a security risk 

assessment by the Attorney General. 

* * * * * 

(l) A registered individual or entity 

transferring an amount of a HHS toxin 

otherwise excluded under the 

provisions of § 73.3(d) of this part must: 

(1) Transfer the HHS toxin only after 

using due diligence and documenting 

that the recipient has a legitimate need 

(reasonably justified by a prophylactic, 

protective, bona fide research, or other 

peaceful purpose) to handle or use such 

toxins. The HHS Secretary retains the 

authority to, without prior notification, 

inspect and copy or request the 

submission of the due diligence 

documentation to the CDC. 

(2) Report to CDC any known or 

suspected violation of Federal law or 

suspicious activity related to the toxin. 

16. Section 73.17 is amended as 

follows: 

a. By revising paragraph (a)(1) 

introductory text to read as set forth 

below. 

b. By redesignating paragraphs (a)(2) 

through (a)(6) as paragraphs (a)(3) 

through (a)(7) respectively. 

c. By adding a new paragraph (a)(2) to 

read as set forth below. 

§ 73.17 Records. 

(a) * * * 

(1) An accurate, current inventory for 

each select agent (including viral 

genetic elements, recombinant and/or 

synthetic nucleic acids, and 

recombinant and/or synthetic 

organisms) held in long-term storage 

(placement in a system designed to 

ensure viability for future use, such as 

in a freezer or lyophilized materials), 

including: 

* * * * * 

(2) An accurate, current inventory of 

any animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent (including number and 

species, location, and appropriate 

disposition); 

* * * * * 

17. Section 73.20 is revised to read as 

set forth below. 

§ 73.20 Administrative review. 

(a) An individual or entity may appeal 

a denial, revocation, or suspension of 

registration under this part. The appeal 

must be in writing, state the factual 

basis for the appeal, and be submitted 

to the HHS Secretary within 30 calendar 

days of the decision. 

(b) An individual may appeal a 

denial, limitation, or revocation of 

access approval under this part. The 

appeal must be in writing, state the 

factual basis for the appeal, and be 

submitted to the HHS Secretary within 

180 calendar days of the decision. 

(c) The HHS Secretary’s decision 

constitutes final agency action. 

Dated: September 21, 2011. 

Kathleen Sebelius, 

Secretary. 

[FR Doc. 2011–25427 Filed 9–30–11; 8:45 am] 

BILLING CODE 4163–18–P 


srobinson on DSK4SPTVN1PROD with PROPOSALS2