Vol. 77 Friday, 

No. 194 October 5, 2012 

Part III 

Department of Health and Human Services 

42 CFR Part 73 

Possession, Use, and Transfer of Select Agents and Toxins; Biennial 

Review; Final Rule 


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61084 Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 

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: Final rule. 

SUMMARY: In accordance with the Public 

Health Security and Bioterrorism 

Preparedness and Response Act of 2002, 

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 

republishing that list. As a result of our 

review, we have added Chapare virus, 

Lujo virus, and SARS-associated 

coronavirus (SARS-CoV) to the list of 

HHS select agents and toxins. We have 

also removed from the list of HHS and 

overlap select agents and toxins, or 

excluded from compliance with part 73, 

the agents and toxins described in the 

Executive Summary. Further, in 

accordance with Executive Order 13546, 

‘‘Optimizing the Security of Biological 

Select Agents and Toxins in the United 

States,’’ HHS/CDC has designated those 

select agents and toxins that 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 as ‘‘Tier 1’’ agents; 

established new security requirements 

for entities possessing Tier 1 agents, 

including the requirement to conduct 

pre-access assessments and on-going 

monitoring of personnel with access to 

Tier 1 agents and toxins; and made 

revisions to the regulations to clarify 

regulatory language concerning security, 

training, biosafety, and incident 

response. 

In a companion document published 

in this issue of the Federal Register, the 

United States Department of Agriculture 

(USDA) has made parallel regulatory 

changes. 

DATES: Effective Dates: The amendments 

to §§ 73.1, 73.3 through 73.6, 73.9, 

73.10, 73.13, 73.16, 73.17, and 73.20, of 

Title 42, Code of Federal Regulations are 

effective December 4, 2012. The 

remaining provisions to this final rule 

are effective April 3, 2013. 

Applicability Dates: By December 4, 

2012, all entities that possess SARS, 

Chapare, and Lujo viruses must provide 

notice to CDC regarding their possession 

of these viruses, and by April 3, 2013, 

all previously unregistered entities must 

meet all of the requirements of this part. 

The Final Rule timelines are based on 

the timelines that worked effectively for 

the Federal Select Agent Program 

Interim Final Rules that were published 

in December 2002. If the regulated 

community has concerns about the 

established timeline, they can contact 

Federal Select Agent Program for 

technical assistance. 

Comment Date: Written comments on 

the new information collection 

contained in this final rule should be 

received by October 15, 2012. 

ADDRESSES: Please send written 

comments on the new information 

collection contained in this final rule to 

CDC Desk Officer, Office of Management 

and Budget, Washington, DC 20503 or 

by fax to (202) 395–5806. 

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 final rule is organized 

as follows: 

I. Executive Summary 

II. Changes to 42 CFR Part 73 

A. Modifications to the List of HHS and 

Overlap Select Agents and Toxins 

B. Tiering of Select Agents and Toxins 

C. Responses to Other Proposed Changes 

i. Definitions 

ii. Exclusions 

iii. Toxins 

iv. Exemptions 

v. Responsible Official 

vi. Access to Select Agents and Toxins 

vii. Security 

viii. Security for Tier 1 Agents and Toxins 

ix. Biosafety Plan 

x. Restricted Experiments 

xi. Incident Response 

xii. Training 

xiii. Transfers 

xiv. Records 

xv. Administrative Review 

xvi. Guidance Documents 

xvii. Miscellaneous 

III. Required Regulatory Analyses 

A. Executive Orders 12866 and 13563 

B. Regulatory Flexibility Act 

C. Paperwork Reduction Act of 1995 

D. Executive Order 12988: Civil Justice 

Reform 

E. Executive Order 13132: Federalism 

F. Plain Writing Act of 2010 

IV. References 

I. Executive Summary 

We published an Advance Notice of 

Proposed Rulemaking (ANPRM) (75 FR 

42363) on July 21, 2010 and a Notice of 

Proposed Rulemaking (NPRM) (76 FR 

61206) on October 3, 2011. The NPRM 

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. In addition, Executive 

Order 13546 ‘‘Optimizing the Security 

of Biological Select Agents and Toxins 

in the United States’’ directed the HHS 

Secretary 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 for these 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. 

We provided a 60-day comment 

period for written comments that ended 

December 2, 2011. We extended the 

comment period for an additional 30- 

day period that ended January 17, 2012. 

The changes to the current regulations 

include: 

1. Modification of the select agent and 

toxin list: 

a. The following viruses are added to 

the HHS select agent list based on 

scientific data related to their significant 

public health risk: SARS-CoV, Lujo and 

Chapare viruses. 

b. The following agents would no 

longer be considered HHS select agents 

or toxins, or would be excluded from 

compliance with part 73: 

Cercopithecine Herpesvirus 1 (Herpes B 

virus), Clostridium perfringens epsilon 

toxin, Coccidioides posadasii/ 

Coccidioides immitis, Eastern Equine 

Encephalitis virus (South American 

type only), Flexal virus, West African 

clade of Monkeypox virus, Rickettsia 

rickettsii, the non-short, paralytic alpha 

conotoxins containing the following 

amino acid sequence 


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1C = Cysteine residues (indicated in bold) are all 

present as disulfides, with the 1st and 3rd Cysteine, 

and the 2nd and 4th Cysteine forming specific 

disulfide bridges; The consensus sequence includes 

known toxins a-MI and a-GI (shown above) as well 

as a-GIA, Ac1.1a, a-CnIA, a-CnIB; X1 = any amino 

acid(s) or Des-X; X2 = Asparagine or Histidine; P 

= Proline; A = Alanine; G = Glycine; X3 = Arginine 

or Lysine; X4 = Asparagine, Histidine, Lysine, 

Arginine, Tyrosine, Phenylalanine or Tryptophan; 

X5 = Tyrosine, Phenylalanine, or Tryptophan; X6 

= Serine, Threonine, Glutamate, Aspartate, 

Glutamine, or Asparagine; X7 = Any amino acid(s) 

or Des X; and ‘‘Des X’’ = ‘‘an amino acid does not 

have to be present at this position.’’ For example 

if a peptide sequence were XCCHPA then the 

related peptide CCHPA would be designated as DesX. 

X1CCX2PACGX3X4X5X6CX7, 1

Shigatoxins, Shiga-like ribosome 

inactivating proteins, Staphylococcal 

Enterotoxins (non-A, non-B, non-C, nonD, and non-E subtypes), and Tick-borne 

encephalitis complex viruses (Central 

European subtype). 

c. The following agent would no 

longer be considered an overlap select 

agent: Venezuelan Equine Encephalitis 

Virus (subtypes ID and IE). 

2. Tiering of the select agent and toxin 

list: 

a. Tier I agents: 

i. HHS select agents and toxins 

(1) Ebola virus 

(2) Francisella tularensis 

(3) Marburg virus 

(4) Variola major virus 

(5) Variola minor virus 

(6) Yersinia pestis 

(7) Botulinum neurotoxin 

(8) Botulinum neurotoxin producing 

species of Clostridium 

ii. Overlap select agents and toxins 

(1) Bacillus anthracis 

(2) Burkholderia mallei 

(3) Burkholderia pseudomallei 

3. Establishing physical security 

standards for entities possessing Tier I 

select agents and toxins, including the 

requirement to conduct pre-access 

assessments and on-going monitoring of 

personnel with access to Tier 1 agents 

and toxins; 

4. Miscellaneous revisions to the 

regulations to clarify regulatory 

language concerning security, training, 

biosafety, and incident response. 

Costs of the Rule: The entities that 

will be affected by the final rules 

include research and diagnostic 

facilities; Federal, State, and university 

laboratories; and private commercial 

and non-profit enterprises. The 

regulations require registering the 

possession, use, and transfer of select 

agents or toxins. In addition, the entity 

is required to ensure that the facility 

where the agent or toxin is housed has 

adequate biosafety and containment 

measures, that the physical security of 

the premises is adequate, that all 

individuals with access to select agents 

or toxins have the appropriate 

education, training, and/or experience 

to handle such agents or toxins, and that 

complete records concerning activities 

related to the select agents or toxins are 

maintained. 

The final rules will further reduce or 

minimize the risk of misuse of select 

agents and toxins that have the potential 

to pose a severe threat to human, animal 

or plant health, or to animal or plant 

products. The USDA/Animal and Plant 

Health Inspection Service (APHIS) and 

HHS/CDC recognize that several of the 

required measures of the regulations 

may impose certain operational costs 

upon affected entities, particularly 

entities that have the newly designated 

Tier 1 select agents and toxins. In many 

cases, however, the affected entities 

already employ some or all of the 

required measures. Compliance costs 

actually incurred will therefore vary 

from one entity to the next. 

While information on the specific 

changes that would need to occur at 

individual sites and the associated costs 

was not readily available during 

proposed rulemaking, some general 

observations regarding the potential 

costs were presented. These general cost 

observations can be found in table 2 in 

the Regulatory Impact Analysis located 

at: www.regulations.gov and at http:// 

www.selectagents.gov/. 

Benefits of the Rule: The objectives of 

the final rules are to create a means of 

ensuring enhanced oversight in the 

transfer, storage, and use of select agents 

and toxins; define the security 

procedures and suitability assessments 

for pre-access suitability and continual 

monitoring of individuals with access to 

Tier 1 select agents and toxins; and 

require that entities in possession of 

such agents and toxins develop and 

implement effective means of biosafety, 

information security, and physical 

security. The overall benefit of the 

amended provisions will be a reduced 

likelihood of the accidental or 

intentional release of a select agent or 

toxin and the avoidance of costs 

associated with such a release. The goal 

of the amended regulations is to 

enhance the protection of human, 

animal, and plant health and safety. 

II. Changes to 42 CFR Part 73 

The table below describes the changes 

to the current regulation. 

Section No. Current Change 

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

73.1 .................... Definitions ................................................ Definitions added: Conotoxins; Information security; Occupational exposure; Recombinant nucleic acids; Security barrier; and Synthetic nucleic acids. 

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. 

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; clarifies language. 

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

and toxins.

Amends the immediate notification list to Tier 1 agents; clarifies language. 

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

73.8 .................... Denial, revocation, or suspension of registration.No change. 

73.9 .................... Responsible Official ................................. Adds new paragraph (a)(5); clarifies language. 

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

toxins; security risk assessments.

Adds new paragraph (e); adds clarifying language. 

73.11 .................. Security .................................................... Revises regulatory text—paragraph (b), (c)(2),(g). Adds new paragraphs (c)(8), 

(c)(9), (c)(10), (e), (f). 

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

paragraph (d). 


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Section No. Current Change 

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

73.14 .................. Incident response .................................... Revises paragraphs (a), (b); adds new paragraphs (c) and (e). 

73.15 .................. Training .................................................... Revises paragraph (a); redesignates and revises paragraphs (b), (c); adds new 

paragraph (b). 

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

73.17 .................. Records ................................................... Revises paragraph (a)(1); 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 and 

Overlap Select Agents and Toxins 

The changes to the list of HHS select 

agents and toxins are based on 

comments received in response to the 

NPRM, recommendations from the 

Federal Experts Security Advisory Panel 

(FESAP) and HHS/CDC’s 

Intragovernmental Select Agents and 

Toxins Technical Advisory Committee 

(ISATTAC), and our review of current 

scientific literature. 

Executive Order 13546 established the 

FESAP to advise the HHS Secretary on 

the designation of Tier 1 agents and 

toxins, the reduction in the number of 

agents on the select agent list, the 

establishment of appropriate practices 

to ensure reliability of personnel with 

access to Tier 1 agents, and the 

establishment of the appropriate 

practices for physical security and cyber 

security for facilities that possess Tier 1 

agents. 

The ISATTAC was established by the 

CDC Director and is comprised of 

Federal government employees from the 

CDC, the National Institutes of Health 

(NIH), the Food and Drug 

Administration (FDA), the Biomedical 

Advanced Research and Development 

Authority (BARDA) within the HHS 

Office of the Assistant Secretary for 

Preparedness and Response (HHS/ 

ASPR), the USDA/APHIS, USDA/ 

Agricultural Research Service (ARS), 

USDA/CVB (Center for Veterinary 

Biologics), the Department of Homeland 

Security (DHS), and the Department of 

Defense (DOD). The purpose of the 

ISATTAC is to assist CDC’s Division of 

Select Agents and Toxins in performing 

its regulatory functions under the select 

agent regulations, including conducting 

a review of the select agents and toxins 

list. 

We received 113 comments that 

addressed the composition of the select 

agents and toxins list. 

As discussed below, the final rule 

removes or excludes 13 select agents 

and toxins, added 3 select agents, and 

designated 11 select agents and toxins 

as ‘‘Tier 1’’ agents. 

HHS Select Agents and Toxins 

Addition of Chapare and Lujo Viruses 

On August 19, 2009, we proposed 

adding the haemorrhagic fever virus 

Chapare, to the list of select agents (74 

FR 41829). 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). 

On October 3, 2011, we proposed 

adding the haemorrhagic fever virus 

Lujo to the list of select agents (76 FR 

61206). According to available reports, 

Lujo virus (1) caused a fatal outbreak of 

hemorrhagic fever, (2) has a case fatality 

rate of 80 percent, (3) has been 

phylogenetically identified as an 

arenavirus, and (4) is related to those 

members of the Old World arenaviridae 

family (Junin, Machupo, Sabia, 

Guanarito, and Lassa) listed as HHS 

select agents that cause hemorrhagic 

fever and pose a significant risk to 

public health and safety (Ref 2). 

Some commenters argued that there 

does not appear to be valid evidence 

that these viruses could be effectively 

utilized as terrorism agents. Another 

commenter recommended that all 

hemorrhagic arenaviruses be included 

in the select agent list. 

We made no changes to the HHS list 

of select agents and toxins based on 

these comments. Although the literature 

on these newly described viruses is 

small and recent, both viruses have thus 

far produced high morbidity and 

mortality rates. Both Lujo and Chapare 

virus share other characteristics with 

regulated hemorrhagic fever viruses 

(Junin, Machupo, Sabia, Guanarito, and 

Lassa). As a taxonomic group, the 

hemorrhagic arenaviruses exhibit 

distinct differences in morbidity, 

mortality, transmissibility, and degree of 

pathogenicity. Therefore our 

consideration of whether to add a 

particular arenavirus to the list is made 

on a taxon-by-taxon basis. As more 

information becomes known about the 

public health risks of these two new 

hemorrhagic fever viruses, their status 

as select agents can be reassessed. 

Individuals and entities that currently 

possess Chapare or Lujo virus, if they 

are not already registered entities, will 

have to either transfer the organism or 

genomic material to a registered entity, 

destroy their stocks and report the 

destruction to HHS/CDC, or if they 

choose to retain their stocks, register 

with HHS/CDC and comply with all 

applicable regulations as provided in 

this final rule. We also recognize that 

those entities that choose to become 

registered will need time to come into 

full compliance with the requirements 

of the regulations. This final rule will 

become effective on December 4, 2012. 

On and after that date, any individual or 

entity possessing, using, or transferring 

any listed select agent or toxin must be 

in compliance with the provisions of 

each part. However, to minimize the 

disruption of critical research or 

educational projects involving Chapare 

or Lujo virus that are underway as of the 

effective date of these regulations, we 

are providing that any individual or 

entity possessing Chapare or Lujo virus 

as of the effective date (current 

possessors) will be afforded additional 

time to reach full compliance with the 

regulations in each part. Accordingly, 

by December 4, 2012, all entities that 

possess Chapare and/or Lujo virus must 

provide notice to HHS/CDC regarding 

their possession of Chapare and/or Lujo 

virus, and by April 3, 2013, all 

previously unregistered entities must 

meet all of the requirements of this part. 

Addition of SARS-Associated 

Coronavirus (SARS-CoV) 

SARS-CoV is associated with one of 

the most significant pandemics of the 

21st century. According to the World 

Health Organization, the 2002–2003 

SARS pandemic involved 29 countries, 

produced over 8000 cases of disease, 

and resulted in 774 deaths (Ref 3). Since 

the end of the pandemic the majority of 

reported SARS-CoV infections have 

occurred in laboratorians, or individuals 

who had close contact with infected 

laboratorians (Ref 4–6). At least 13 (6 

primary cases and 7 contacts) 


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individuals have contracted laboratoryassociated SARS-CoV infections (Ref 7). 

On July 13, 2009, we proposed the 

addition of SARS-CoV to the list of 

select agents and toxins (74 FR 33401). 

We received ten comments from 

representatives of universities, public 

health laboratories, commercial, and 

government facilities, all arguing that 

SARS-CoV should not be added to the 

select agent list. Commenters believed 

that further deliberation of the biosafety 

and biosecurity issues involved with 

this agent should be considered due to 

the implications for research and public 

health activities. The commenters 

further reasoned that adding SARS-CoV 

as a select agent would decrease public 

safety and security by preventing expert 

researchers from pursuing important 

work due to what they described as the 

additional costs and onerous burdens 

inherent with the select agent 

registration and compliance process. 

During the public comment period for 

this rulemaking we received three 

comments from representatives from 

universities and a public health 

laboratory that recommended the 

addition of SARS-CoV to the list of 

select agents and toxins because (1) it 

exhibited high transmissibility and high 

lethality; (2) caused epidemics on four 

continents with significant mortality; (3) 

had a major economic impact; and (4) 

had a major psychological impact. 

Commenters further argued that the 

virus has demonstrated its ability to 

cause a contagious disease, has caused 

several laboratory infections (including 

one incident that led to cases in nonlaboratory contacts) and is a virus which 

no longer circulates in nature. 

We agree with the commenters who 

supported the addition of SARS-CoV to 

the list of select agents and toxins 

because of the significant impact of 

SARS-CoV on the public health system, 

the high degree of pathogenicity, and 

the lack of vaccines or proven 

therapeutics currently available to 

prevent or treat SARS-CoV infections. 

Additionally, we note that the virus no 

longer appears to be naturally 

circulating in humans, raising the 

concern that the general population 

does not possess a significant level of 

immunity. 

The genome of SARS-CoV will be 

regulated as an HHS select agent. As a 

member of the Coronarviridae family, 

SARS-CoV is an enveloped virus with a 

positive-sense RNA genome. Positivesense RNA viruses that utilize host 

polymerases contain nucleic acids, in 

and of themselves, that can produce 

infectious forms of the virus. The select 

agent regulations apply to nucleic acids 

that can produce infectious forms of any 

of the select agent viruses (See section 

3(c) of 42 CFR part 73, 9 CFR part 121, 

and 7 CFR part 331). 

Based on information received from 

the HHS/CDC’s Etiologic Agent Import 

Permit Program and the HHS/CDC’s 

Office of Infectious Diseases, there are 

119 entities that currently possess 

SARS-CoV. Of those 119 entities, 77 

entities are registered with the Federal 

Select Agent Program; 42 entities are not 

registered. Of the 42 non-registered 

entities, only 38 may possess SARS-CoV 

or SARS-CoV genomic material (RNA). 

The 38 non-registered entities that may 

possess SARS-CoV or SARS-CoV 

genomic material (RNA) include 10 

academic, 22 commercial, 5 State 

government, and 1 Federal government 

institutions. 

Entities and individuals that currently 

possess SARS-CoV or SARS-CoV 

genomic material (RNA) will have to 

either (1) transfer the organism or 

genomic material to a registered entity; 

(2) destroy their stocks and report the 

destruction to CDC; or (3) register with 

HHS/CDC or USDA/APHIS to possess 

SARS-CoV and comply with all 

applicable regulations as provided in 

this final rule. We also recognize that 

those entities that choose to become 

registered with the Federal Select Agent 

Program will need time to come into full 

compliance with the requirements of the 

regulations. Since this final rule will 

become effective on December 4, 2012 

and any individual or entity possessing, 

using, or transferring any listed agent or 

toxin must be in compliance with the 

provisions of each part on or after that 

date, we are providing that any 

individual or entity possessing SARSCoV as of the effective date (current 

possessors) will be afforded additional 

time to reach full compliance with the 

regulations in each part. Accordingly, 

by December 4, 2012, all entities that 

possess SARS-CoV must provide notice 

to HHS/CDC regarding their possession 

of SARS-CoV, and by April 3, 2013, all 

previously unregistered entities must 

meet all of the requirements of this part. 

We are extending the effective date for 

these currently non-registered entities to 

minimize the disruption of critical 

research or educational projects 

involving SARS-CoV that are underway 

as of the effective date of these 

regulations. 

Removal of Cercopithecine Herpesvirus 

1 (Herpes B Virus) 

We are removing Cercopithecine 

herpesvirus 1 (Herpes B virus) from the 

HHS list of select agents and toxins. We 

proposed the removal of Cercopithecine 

herpesvirus 1 (Herpes B virus) from the 

HHS list of select agents and toxins 

because the 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. The only comments that we 

received on this proposal were 

supportive for the removal. 

Removal of Clostridium Perfringens 

Epsilon Toxin 

The proposed rule retained C. 

perfringens epsilon toxin on the list of 

select agents and toxins. The final rule 

removes it. Commenters questioned 

why C. perfringens epsilon toxin was 

listed as a select agent since its 

production is licensed by USDA under 

the Virus-Serum-Toxin Act. In addition, 

commenters argued that from a 

veterinary laboratory perspective, C. 

perfringens epsilon toxin is commonly 

detected in the gastrointestinal tract 

during routine post-mortem diagnostic 

testing and the quantity of toxin 

recovered from a positive diagnostic 

sample would be far below the 100 mg 

exclusion amount provided for in the 

select agent regulations. Commenters 

also supplied scientific data in support 

of removal of C. perfringens epsilon 

toxin from the select agent and toxin list 

(Ref 8). 

Although many of the concerns raised 

by the commenters are addressed by the 

exemption and exclusion provisions in 

the regulations (42 CFR 73.3 and 73.5), 

we agree with commenters and have 

determined that C. perfringens epsilon 

toxin should be removed from the list of 

HHS select agents and toxins. C. 

perfringens epsilon toxin was originally 

included on the select agent list because 

of its relatively low (LD)50 (lethal dose 

fifty: the amount of the toxin required 

to kill 50 percent of the test population) 

in rodents and moderate toxicity when 

in aerosol form. The LD50 results for C. 

perfringens epsilon toxin are based on a 

mouse in vivo injection model, which 

does not completely mimic a natural 

infection, and therefore may not 

accurately represent the human LD50.

Additional significant factors in our 

determination to remove C. perfringens 

epsilon toxin include the absence of 

known human cases of disease, a lack of 

human or non-human primate toxicity 

data, and insufficient new data to 

indicate that C. perfringens epsilon 

toxin is a significant threat to public 

health and safety. 

Reduction of Conotoxins on the HHS 

List of Select Agents and Toxins 

The term ‘‘conotoxin’’ is used broadly 

to comprise a very large number of 

polypeptides isolated from the venom of 


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fish-hunting marine snails of the Conus 

genus of gastropod mollusks. Many of 

these molecules are neurologically 

active in mammals. Although we did 

not propose the removal for conotoxins, 

we did receive multiple comments that 

conotoxins should be removed from the 

list of select agents and toxins for the 

following reasons: 

• Commenters noted that most 

components isolated from cone snail 

venom are harmless to humans; in fact, 

one of them (MVIIA = Ziconotide = 

PrialtTM) is an FDA-approved 

commercial drug for the treatment of 

chronic pain. Several other 

conopeptides have reached clinical 

trials at various levels (CVID, 

Conantokin-G, Contulakin-G, Xe2174 

and ACV1 = a conotoxin Vc1.1), and 

they all show extremely low levels of 

toxicity to humans. 

• Commenters pointed to the fact that 

the term ‘‘conotoxin’’ can be applied to 

several hundred thousand compounds 

found in Conus venoms that are not 

toxic at all to humans is evidence that 

this designation needs to be revised. 

Furthermore, the designation of 

‘‘conotoxins’’ as select toxins imposes 

an enormous and unnecessary burden 

for the development of cone snail-based 

therapeutics. 

Other comments included the 

following: 

• Conotoxins have never been 

weaponized. 

• Conotoxins must be delivered 

parenterally. 

• Conotoxins are difficult to 

manufacture. 

• Conotoxins are not self-replicating. 

We agree, in part, with the 

commenters. Based upon available 

experimental evidence, most known 

conotoxins (i.e., ‘‘conopeptides’’) do not 

possess sufficient acute toxicity to pose 

a significant public health threat, and 

many are employed as useful research 

tools or potential human therapeutics. 

However, currently available data 

demonstrate that the sub-class of 

conotoxins generally called ‘‘short, 

paralytic alpha conotoxins,’’ 

exemplified by a-conotoxin GI and aconotoxin MI do possess sufficient acute 

toxicity by multiple routes of exposure, 

biophysical stability, ease of synthesis, 

and availability. Therefore, we have 

modified the type of conotoxins that are 

regulated to focus on those that pose a 

threat to public health and safety. The 

conotoxins that remain on the HHS list 

will be limited to the short, paralytic 

alpha conotoxins containing the 

following amino acid sequence 

X1CCX2PACGX3X4X5X6CX7, whereas: 

(a) C = Cysteine residues (indicated in bold) 

are all present as disulfides, with the 1st 

and 3rd Cysteine, and the 2nd and 4th 

Cysteine forming specific disulfide 

bridges; 

(b) The consensus sequence includes known 

toxins a-MI and a-GI (shown above) as 

well as a-GIA, Ac1.1a, a-CnIA, a-CnIB 

(c) X1 = any amino acid(s) or Des-X; 

(d) X2 = Asparagine or Histidine; 

(e) P = Proline; 

(f) A = Alanine; 

(g) G = Glycine; 

(h) X3 = Arginine or Lysine; 

(i) X4 = Asparagine, Histidine, Lysine, 

Arginine, Tyrosine, Phenylalanine or 

Tryptophan; 

(j) X5 = Tyrosine, Phenylalanine, or 

Tryptophan; 

(k) X6 = Serine, Threonine, Glutamate, 

Aspartate, Glutamine, or Asparagine; 

(l) X7 = Any amino acid(s) or Des X; and 

(m) ‘‘Des X’’ = ‘‘an amino acid does not have 

to be present at this position.’’ For 

example if a peptide sequence were 

XCCHPA then the related peptide 

CCHPA would be designated as Des-X. 

The short, paralytic alpha conotoxins 

containing the following amino acid 

sequence X1CCX2PACGX3X4X5X6CX7

will be considered a select toxin if the 

total amount (all forms) under the 

control of a principal investigator, 

treating physician or veterinarian, or 

commercial manufacturer or distributor 

exceeds 100 mg at any time (Ref 9–13). 

As such, we have added the definition 

of regulated conotoxins. 

Removal of Coccidioides Posadasii/ 

Coccidioides Immitis 

We are removing C. posadasii/C. 

immitis from the HHS list of select 

agents and toxins. We proposed the 

removal of C. posadasii/C. immitis 

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 14). The only 

comments that we received on this issue 

were supportive of the removal of C. 

posadasii/C. immitis from the HHS list 

of select agents and toxins. 

Removal of Flexal Virus 

We are removing Flexal virus from the 

HHS list of select agents and toxins. We 

proposed the removal of Flexal virus 

based on the lack of severity of disease 

and the lack of significant outbreaks of 

disease associated with this virus in 

humans. The only comments that we 

received on this issue were supportive 

of the removal of Flexal virus from the 

HHS list of select agents and toxins. 

Removal of the West African Clade of 

Monkeypox Virus 

We are excluding the West African 

clade of Monkeypox from regulation 

under this part, while retaining the 

Congo Basin clade of Monkeypox. We 

proposed the retention of Monkeypox 

on the list of select agents and toxins, 

but invited comments on removing the 

West African clade of Monkeypox virus 

from the list. Monkeypox is closely 

related to smallpox virus and produces 

a clinical syndrome similar to that seen 

with smallpox. Mortality rates 

associated with Monkeypox infections 

have been reported to be as high as 17 

percent (Ref 15–16). Monkeypox can be 

separated into two genetically distinct 

variants called the West African and 

Congo Basin clades. Clinical and 

laboratory studies indicate that the 

Congo Basin clade is significantly more 

pathogenic to humans and animals than 

the West African clade (Ref 17–18). The 

37 confirmed cases of human 

Monkeypox associated with the 2003 

importation of a West African strain 

from Ghana into the United States were 

associated with no case-fatalities and no 

observed chain of human-to-human 

transmission. Clinically severe human 

disease associated with West African 

strains is rare and this virus clade has 

not been associated with human 

mortality (Ref 19). Based on this 

information, we are excluding the West 

African clade from regulation under this 

part, while retaining the Congo Basin 

clade. 

One commenter disagreed with the 

proposed retention of Monkeypox virus, 

regardless of clade, as a select agent. We 

agreed in part with the commenter. As 

indicated above, we recognize that 

significant differences in pathogenicity 

exist between the West African and 

Congo Basin clades and have 

determined that viruses of only the 

Congo Basin clade merit regulation as 

HHS select agents. We also note that 

there are published diagnostic tests that 

differentiate Congo Basin from West 

African clades (Ref 19). 

While the listing found in section 3 

(HHS select agents and toxins) will 

continue to read ‘‘Monkeypox’’, a new 

subparagraph (d)(5) in that same 

section, excludes from regulation any 

West African clade of the Monkeypox 

virus provided that an individual or 

entity can verify that the Monkeypox 

virus is the West African clade. 

Removal of South American Genotypes 

of Eastern Equine Encephalitis Virus 

(EEEV) 

We proposed the removal of South 

America EEEV genotypes from the list of 

HHS select agents and toxins and the 

final rule is consistent with the 

proposed rule. 

One commenter believed that all 

strains of EEEV should be removed from 


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the select agent list for the following 

reasons: 

• The commenter noted that EEEV is 

endemic in Florida, but does not cause 

human epidemics even with high 

prevalence in the ecosystem and 

evidence of natural transmission 

activity to sentinels. 

• The commenter noted that personto-person transmission does not occur; 

transmission is only through mosquito 

bite. An average of only 5 human cases 

are identified annually in the United 

States. 

• The commenter noted that there is 

a vaccine available for horses that can 

prevent disease even if there is ongoing 

natural virus transmission. 

• The commenter noted that states 

with high endemicity of EEEV often 

have a state public health laboratory 

proactive comprehensive arbovirus 

surveillance program to define risk of 

human infection. Serum-neutralization 

assays are an essential part of such a 

program and require live virus which is 

needed for test performance. This work 

is performed at BSL3 level and 

additional federal regulatory 

requirements do not add to the safety of 

handling or storing the virus. 

• The commenter noted that genotype 

analysis to determine if an EEEV strain 

is a North American or South American 

genotype is not practical in a state 

public health laboratory, where the goal 

is surveillance, not research. 

• The commenter noted that this 

agent is not stable in the environment 

outside of its natural host (mosquitoes, 

birds). 

We made no changes to the list of 

HHS select agents and toxins based on 

this comment. North American EEEV 

(NA EEEV), genotype strains, which are 

the strains responsible for human and 

equine disease, are all genetically very 

similar to each other (less than 3 percent 

divergence at the nucleotide level) and 

can be easily distinguished from South 

American EEEV (SA EEEV) genotype 

strains by sequencing. NA EEEV 

genotype strains differ from SA EEEV by 

greater than 20 percent at the nucleotide 

level and approximately 10 percent at 

the amino acid level. We are aware that 

EEEV is endemic in Florida, that 

person-to-person transmission does not 

occur, that an equine vaccine is 

available, and that EEEV isn’t stable 

outside of its natural host. Among the 

factors that we considered in retaining 

the NA EEEV genotype were that this 

genotype exhibits high morbidity, high 

mortality, and has the potential to be 

weaponized. We also appreciate that 

public health laboratories focus on 

surveillance and utilize assays that do 

not specifically determine which 

subtype of EEEV is present. However, 

we believe that the risks posed by the 

NA EEEV outweigh the practical issues 

associated with subtype determination. 

Because the NA EEEV genotype strains 

are distinctly different from SA EEEV in 

their genetics, epidemiology, and 

pathogenicity, we believe that the two 

genotypes can be distinguished from 

each other in the laboratory. 

While the listing found in section 3 

(HHS select agents and toxins) will 

continue to read ‘‘Eastern Equine 

Encephalitis virus,’’ a new subparagraph 

(d) (5) in that same section excludes 

from regulation, any South American 

genotypes of Eastern Equine 

Encephalitis virus provided that an 

individual or entity can verify that the 

Eastern Equine Encephalitis virus is one 

of the South American genotypes. 

Rickettsia prowazekii and Rickettsia 

rickettsii 

The proposed rule retained R. 

rickettsii and R. prowazekii on the HHS 

list of select agents and toxins. The final 

rule removes R. rickettsii and retains R. 

prowazekii. 

Commenters argued that R. rickettsii 

and R. prowazekii should be removed 

from the select agent list based on: 

• The same rationale used by HHS/ 

CDC to propose removal of Herpes B 

virus from the HHS select agent list; 

• R. rickettsii and R. prowazekii are 

readily available in nature, and can be 

isolated from natural sources such as 

ticks and flying squirrel lice; 

• R. rickettsii and R. prowazekii are 

not contagious; 

• Human infections due to these 

agents are capable of being treated with 

doxycycline, other tetracyclines, and 

chloramphenicol; 

• The bacteria are fastidious obligate 

intracellular pathogens, thus 

propagation requires growth in cultured 

host cells; and 

• The inclusion of these rickettsiae on 

the HHS select agent list will produce 

no significant improvements in safety 

for the American public. 

After careful consideration of these 

comments, we agree with the 

commenters that R. rickettsii should be 

removed from the HHS list of select 

agents and toxins. Significant factors in 

our reconsideration include the poor 

environmental stability of this species, 

the lack of person-to-person 

transmission especially in the absence 

of an appropriate vector, the availability 

of effective antibiotic treatments, and 

the difficulty in growing and purifying 

substantial quantities of these agents in 

vitro. However, we have determined 

that R. prowazekii should be retained as 

a select agent. This species was 

investigated as a potential weapon by 

multiple national offensive programs 

prior to the Biological Weapons 

Convention, and has many 

characteristics of a bioweapon. The 

infectious dose for R. prowazekii is 

unknown but has been estimated to be 

as little as 10 organisms (Ref 20). There 

are currently no licensed vaccines 

against R. prowazekii available for 

human use in the United States. Until 

additional studies can be completed to 

better understand the potential risk of 

an intentional release of this organism 

to the public, we have determined to 

retain R. prowazekii on the HHS Select 

Agent List. 

Removal of Shigatoxins and Shiga-Like 

Ribosome Inactivating Proteins 

We proposed the retention of 

Shigatoxins and Shiga-like ribosome 

inactivating proteins on the HHS list of 

select agents and toxins. One 

commenter asked us to reconsider the 

retention of Shigatoxins and Shiga-like 

ribosome inactivating proteins as a 

select toxin based on the following 

criteria: 

• Introduction of Shigatoxins by the 

aerosol route has not been reported; 

• Shigatoxins are extremely difficult 

to synthesize in quantities that are toxic 

to humans; 

• Expression of toxin in bacteria is 

self-limiting due to inhibitory effects on 

bacterial cells of over-expressed toxin; 

and 

• There are limitations to purification 

and concentration of Shigatoxins that 

make them impractical and ill-suited to 

methods of dispersal that would require 

large quantities of toxin for delivery by 

food, water, or air. 

We have considered all of the points 

raised by the commenter and, after 

additional consultations with subject 

matter experts, agree that compelling 

data exist to support the removal of 

Shigatoxin and Shiga-like ribosome 

inactivating proteins from the HHS list 

of select agents and toxins. Therefore, 

we have decided to remove Shigatoxin 

and Shiga-like ribosome inactivating 

proteins from the HHS list of select 

agents and toxins. Additional significant 

factors considered in our determination 

include the difficulty in producing or 

administering large quantities of toxin 

via the aerosol route, their poor 

environmental stability, the lack of 

significant toxicity seen with oral 

exposure (which is the route by which 

an individual becomes intoxicated by 

Shigatoxin), and the observation that the 

worst effects seen with intoxication are 

associated with other pathogenic factors 

from the Shigatoxin-producing strains of 

E. coli, which are not regulated. 


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Reduction of Staphylococcal 

Enterotoxins on the HHS List of Select 

Agents and Toxins 

We proposed the reduction of 

Staphylococcal Enterotoxins on the 

HHS list of select agents and toxins to 

only include Staphylococcal 

Enterotoxins A, B, C, D, and E. 

Commenters were concerned that the 

‘‘incredible simplicity’’ of obtaining 

Staphylococcal species from 

environmental sources and screening 

them for the presence of enterotoxins 

‘‘utterly neuters’’ the intent of the select 

agent regulations to provide security 

against the misuse of such agents. A 

commenter requested ‘‘CDC to consider 

alternative regulatory strategies to 

balance the need of legitimate scientific 

access to such agents so that it is not 

harder to use them than for a terrorist.’’ 

We made no changes to the HHS list 

of select agents and toxins based on this 

comment. Current data based on emesis 

in non-human primates demonstrates 

that Staphylococcal Enterotoxins A, B, 

C, D, and E pose a significant threat to 

public health and safety. In addition, we 

note that these enterotoxins exhibit 

significant environmental stability, 

which contributes to their public health 

risk. It should be noted that this revision 

represents a significant reduction of the 

types of Staphylococcal enterotoxins 

regulated as HHS select toxins. 

Reorganization of Tick-Borne 

Encephalitis Complex Viruses (TBEV) 

We proposed the removal of TBEV 

Central European subtype from the HHS 

list of select agents and toxins because 

the TBEV Central European Tick-borne 

subtype has been shown to be less 

virulent in humans than the Far Eastern 

subtype (Ref 21). We also proposed 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 22). 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 proposed 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. 

All comments that we received on this 

issue were supportive of the removal of 

TBEV Central European subtype from 

the HHS list of select agents and toxins 

and the reorganization of the listing of 

the TBEV to reflect the current 

nomenclature. 

Retention of Coxiella burnetii 

We proposed the retention of C. 

burnetii on the HHS list of select agents 

and toxins. Commenters argued that this 

agent should be removed because: 

• This organism is ubiquitous in the 

United States, and can be detected in 

greater than 90 percent of bulk milk 

tank samples. Despite this, significant 

human consequences to infection with 

this agent are rare. 

• The organism is readily susceptible 

to available antibiotics. 

While perhaps easily transmitted to 

humans, the disease caused by this 

organism is generally mild and selflimiting in humans and does not have 

a huge economic impact in animals. It 

therefore does not have the potential to 

be an effective terrorist weapon. We 

made no changes to the HHS list of 

select agents and toxins based on these 

comments. We recognize that there is a 

low level of mortality associated with 

this agent; that it is present in some bulk 

unpasteurized milk supplies; and that 

antibiotics are available to treat this 

disease. However, treatment of chronic 

Q fever caused by C. burnetii requires 

antibiotic regimens that can last for 

periods up to several years. This longterm treatment is associated with 

significant adverse effects and relapse is 

common upon withdrawal of the 

treatment (Ref 23). The determination to 

retain C. burnetii on the HHS list of 

select agents and toxins is based on 

multiple factors, including its 

environmental stability, ease of 

transmission to humans, extremely low 

infectious dose, high morbidity, its 

ability to incapacitate large numbers of 

people, and its prior history of 

weaponization. Historical records 

indicate that extensive development 

occurred in the use of this agent as an 

incapacitating weapon. 

Retention of Diacetoxyscirpenol, 

Saxitoxin, T–2, and Tetrodotoxin 

Toxins 

We proposed the retention of 

Diacetoxyscirpenol, Saxitoxin, T–2 

toxin, and Tetrodotoxin on the HHS list 

of select agents and toxins. One 

commenter recommended the removal 

of these toxins along with Shiga-like 

ribosome inactivating proteins, 

Shigatoxin, Conotoxins, and C. 

perfringens epsilon toxin. This 

commenter stated that ‘‘continuing to 

include these toxins on the select agent 

list has unintended consequences such 

as the U.S. Department of 

Transportation (USDOT) policies 

regarding shipment of infectious 

substances that extends the list to 

agents, such as E. coli that produce 

these toxins, which results in limiting 

shipments to public health 

laboratories.’’ 

Although Shigatoxin producing 

strains of Escherichia coli are not 

subject to the select agent regulations, 

the removal of Shigatoxin and Shigalike ribosome inactivating proteins 

should positively address the 

commenter’s concern regarding the 

USDOT policies. We do not agree with 

the commenter that Saxitoxin, T–2 

toxin, Tetrodotoxin, and 

Diacetoxyscirpenol should be removed 

from the list. Significant factors 

considered in our determination to 

retain these toxins are their acute 

human toxicity, the lack of medical 

countermeasures or specific antidotes, 

and the stability of the toxins in a 

variety of different matrices including 

foodstuffs. 

With respect to the comment 

expressing concerns about the 

regulation of E. coli strains that produce 

these toxins, it should be noted that 

nucleic acids that encode for the 

functional form(s) of select toxins, if the 

nucleic acids can be expressed in vivo 

or in vitro or are in a vector or 

recombinant host genome and can be 

expressed in vivo or in vitro, are subject 

to the regulations (See § 73.3(c)(2)). We 

consider it important to regulate E. coli 

strains that have been modified to 

produce these materials since they are 

capable of producing significant 

quantities of select toxins. It should also 

be noted that E. coli strains that do not 

contain nucleic acids that encode for the 

functional form(s) of select toxins are 

not subject to these regulations. 

Retention of Yersinia pestis 

We proposed to retain Y. 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 Y. 

pestis infections. We received no 

comments regarding this proposal. 

Overlap Select Agents and Toxins 

Reorganization of Venezuelan Equine 

Encephalitis Virus (VEE) 

We proposed the removal of VEE 

subtypes ID and IE from the list of 

overlap select agents and toxins, with 

subtypes IAB and IC being retained on 

the list. Commenters recommended 


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removing the entire VEE group from the 

overlap select agent list because they 

believe that current subtyping assays for 

the identification of VEE are not 

sensitive enough to distinguish between 

these subtypes. One commenter stated 

that the subtype IC group can arise via 

a single mutation in the ID group and 

considering VEE’s high mutation rates, 

an IC subtype can emerge from a 

laboratory using subtype ID strains. 

Commenters also noted that there are 

two vaccines available for humans. In 

addition, commenters argued that the 

mortality rate associated with VEE 

infections via the aerosol route may be 

very low. 

We made no changes to the overlap 

list of select agents and toxins based on 

these comments. Straightforward 

diagnostic molecular techniques, such 

as sequencing with subtype/variety 

specific polymerase chain reaction 

(PCR) primer sets or serological testing 

with specific monoclonal antibodies, 

can distinguish between enzootic and 

epizootic VEE. We also note that based 

on available data, the emergence of 

epidemic subtype 1C from subtype 1D is 

a rare event. In addition, while an 

equine vaccine is available for VEE, 

human vaccines are limited in supply 

and availability. 

While the listing found in section 4 

(Overlap select agents and toxins) will 

read ‘‘Venezuelan equine encephalitis 

virus,’’ a new subparagraph (d)(3) in 

that same section excludes from 

regulation, any ID and IE serotypes of 

Venezuelan equine encephalitis virus 

provided that an individual or entity 

can verify that the Venezuelan equine 

encephalitis virus is either the ID or IE 

serotype. 

Retention of Bacillus anthracis (Pasteur 

Strain) 

We proposed to designate B. anthracis 

as a Tier 1 select agent. A number of 

commenters objected to such a blanket 

designation, arguing instead that the B. 

anthracis Pasteur strain should be 

exempted from consideration either as a 

Tier 1 select agent or as a select agent 

in general. 

Commenters argued that because 

Laboratory Response Network (LRN) 

laboratories maintain live cultures of 

non-pathogenic B. anthracis Pasteur 

strain for use in quality control testing, 

designation of B. anthracis as a Tier 1 

select agent would have the potential to 

impact the willingness or ability of LRN 

laboratories to maintain inventories of 

B. anthracis Pasteur strain due to the 

perceived regulatory and financial 

burdens associated with the possession 

of Tier 1 select agents and toxins. The 

commenters went on to state that this 

situation could potentially impact 

national health and safety given that the 

potential use of B. anthracis spores as a 

bioweapon remains a viable threat. They 

also argued that the increased regulatory 

burdens, particularly on front-line 

diagnostic laboratories, could lead to an 

overall decrease in the number of 

laboratories that would otherwise serve 

to ensure the LRN has sufficient 

capacity to detect and respond to a 

deliberate release of B. anthracis. 

Commenters stated that the B. 

anthracis Pasteur strain is analogous to 

the B. anthracis Sterne strain, which has 

already been excluded pursuant to 

section 4(e) of the select agent 

regulations because it was determined 

not to pose a severe threat to public 

health and safety, animal health, or 

animal products. The commenters 

argued that B. anthracis Pasteur strain 

should not be considered as a select 

agent given that the only way to create 

an agent that poses a severe threat 

would be to combine the Pasteur strain 

with a non-regulated strain. The 

commenters pointed out that other 

agents that pose little harm 

individually, but could be modified 

genetically to become harmful, are not 

included on the select agent list because 

of this potential threat. 

Another commenter claimed that the 

designation of B. anthracis Pasteur 

strain as a select agent would not serve 

to prevent an authorized person from 

intentionally or accidentally facilitating 

the combination of plasmids from 

Sterne and Pasteur types of strains to 

create a wild type phenotype. The 

commenter stated that combining these 

two strains can be accomplished no 

matter what sort of physical security 

may be employed to prevent access, 

theft, loss, or release of the agent. The 

commenter concluded that more 

effective preventive measures can be 

achieved through training and educating 

microbiologists on how to avoid 

accidentally combining these two 

strains and by penalizing any 

individuals who intentionally try to 

combine them. 

We only agree in part with the 

commenters that it does not meet the 

Tier 1 designation, but do not agree to 

removing it from the select agent list 

altogether. 

While we agree that the Pasteur strain 

does not meet the criteria for inclusion 

as a Tier 1 select agent, we believe that 

retaining the Pasteur strain as a select 

agent will allow for continued oversight 

of laboratories in which the accidental 

(or intentional) combination of this 

strain with the Sterne strain could occur 

to produce the wild type phenotype B. 

anthracis de novo. Failure to retain the 

Pasteur strain as a select agent could 

result in an environment in which the 

probability of creating virulent wild 

type B. anthracis strains by the 

combination of non-regulated strains 

would be enhanced. Therefore, we have 

chosen not to exclude the Pasteur strain 

from the overlap list of select agents in 

this rulemaking. We will continue to 

evaluate exclusion requests as 

additional information becomes 

available in this area. 

Retention of Brucella abortus, Brucella 

melitensis, and Brucella suis 

We proposed to retain B. abortus, B. 

melitensis, and B. suis 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 lack of brucellosis 

vaccines currently available for humans 

in the United States. We received no 

comments based on this proposal and 

will be retaining B. abortus, B. 

melitensis, and B. suis on the overlap 

list of select agents and toxins. 

Retention of Burkholderia mallei 

We proposed to retain B. mallei on the 

overlap list of select agents and toxins 

based on our determination that the 

bacteria can be easily produced in large 

quantity and transmitted via the aerosol 

route. In addition, the mortality rate for 

untreated cases of glanders is high, and 

given the rarity of this disease in the 

United States, experience in the 

diagnosis and treatment is limited. We 

received no comments based on this 

proposal and will be retaining B. mallei 

on the overlap list of select agents and 

toxins. 

Retention of Burkholderia pseudomallei 

We proposed the designation of B. 

pseudomallei as a Tier 1 select agent. 

Commenters stated that B. pseudomallei 

should not be a select agent based on 

the following criteria: 

• The criteria by which Coccidioides 

were proposed by HHS/CDC to be 

removed from the list; 

• B. pseudomallei is noncommunicable from person-to-person; 

• B. pseudomallei lacks a history of 

use or development as a successful 

biologic weapon (as compared with B. 

mallei, a highly pathogenic organism 

with which B. pseudomallei is 

inappropriately linked in the list); 

• B. pseudomallei has a low 

incidence of symptomatic disease 

following natural infection; and 

• The outcome of 99.9 percent of 

infections with B. pseudomallei is 

asymptomatic infection. Lifethreatening illness occurs only in a few 


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hosts with particular risk factors, 

particularly renal failure and diabetes. 

We disagree with the commenters that 

B. pseudomallei should be removed 

from the overlap list of select agents and 

toxins. Significant factors in our 

determination include the fact that B. 

pseudomallei is as virulent in animal 

models as B. mallei, B. pseudomallei is 

not endemic in the United States, B. 

pseudomallei has a low infectious dose, 

B. pseudomallei possesses robust 

environmental stability, and timely 

diagnosis may be complicated because 

of the rareness of disease in the United 

States. In addressing the comment 

referring to the criteria used to remove 

Coccidioides, we note 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. We do not believe that these 

factors apply to B. pseudomallei. In 

addition, we note that B. pseudomallei 

is not extensively endemic in the United 

States as are Coccidioides species. 

Therefore, we are retaining B. 

pseudomallei on the overlap list of 

select agents and toxins. 

B. Tiering of Select Agents and Toxins 

On July 2, 2010, President Obama 

signed Executive Order 13546 

‘‘Optimizing the Security of Biological 

Select Agents and Toxins in the United 

States’’ that directed the HHS Secretary 

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. In the development 

of the Tier 1 subset, care was used to 

balance risks identified in Executive 

Order 13546 with the Congressional 

mandate found in the Public Health 

Security and Bioterrorism Preparedness 

and Response Act of 2002 (42 U.S.C. 

262a) to ensure the availability of select 

agents and toxins for research, 

education, and other legitimate 

purposes. Executive Order 13546 also 

established the FESAP to advise the 

HHS Secretary 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 the 

establishment of physical security and 

information security standards for Tier 

1 select agents and toxins. Tiering of the 

select agents and toxins list will allow 

for the application of optimized security 

measures for those select agents or 

toxins which pose a higher risk to 

public health and safety. A two-part risk 

analysis was conducted by the FESAP 

on each select agent and toxin on the 

list. First, experts in the biology of these 

agents and toxins evaluated their 

‘‘potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence.’’ This included assessments 

of morbidity and mortality, 

communicability, infectious dose, 

availability of countermeasures, and 

estimated economic impact of a 

potential attack. Second, each agent and 

toxin was assessed by experts from the 

DOD, DHS, and Department of Justice 

(DOJ) for its ‘‘risk of deliberate misuse,’’ 

including its history of weaponization 

and/or known interest by state or nonstate adversaries. In addition, the 

Federal Select Agent Program also used 

information obtained from DHS Material 

Threat Determinations in making final 

decisions regarding their 

recommendations as to which select 

agent or toxin should be designated as 

Tier 1. These evaluations in 

combination with (1) input from public 

comments received in response to the 

NPRM, and (2) relevant findings in 

recent government and non-government 

reports, informed the deliberations on 

which agents should be designated as 

Tier 1, as well as those that should be 

removed from the select agent and toxin 

list. Agents that scored highly on both 

the public health and biothreat sets of 

criteria were judged to be those that met 

the criteria for Tier 1. We have 

determined that the following agents 

should be designated as Tier 1 agents: 

B. anthracis, Botulinum neurotoxins, 

Botulinum neurotoxin producing 

species of Clostridium, B. mallei, B. 

pseudomallei, Ebola virus, F. tularensis, 

Marburg virus, Variola major virus, 

Variola minor virus, and Y. pestis. 

Commenters questioned why we 

believe that the current regulations were 

not sufficient to contain, secure, and 

protect the proposed Tier 1 select agents 

and toxins from theft, loss, exposure, or 

release. In response, we note that the 

absence of clearly defined, risk-based 

security measures in the select agent 

regulations raised concern both by 

stakeholders within the Executive 

Branch and outside the government. 

This is the focus of Executive Order 

13486 (Strengthening Laboratory 

Biosecurity in the United States) and 

Executive Order 13546 (Optimizing the 

Security of Biological Select Agents and 

Toxins in the United States) that call for 

improvements in select agent security 

and risk management. The additional 

security requirements for those entities 

possessing Tier 1 select agents and 

toxins will enhance physical security, 

personnel suitability, and information 

security within the affected entities. 

The commenters further contended 

that the proposed regulatory changes 

failed to achieve the goal of minimizing 

the impact of the regulations on the 

legitimate uses of select agents and 

toxins that Executive Order 13546 notes 

are essential to national security. In 

response, we note that the overall 

number of select agents and toxins has 

been reduced, lessening the overall 

regulatory burden. In addition, by 

maintaining a performance-based 

approach in the regulations, we are 

allowing regulated entities to develop 

policies and procedures that meet the 

new requirements of the regulations 

while accommodating specific 

operational aspects of each entity. 

Other commenters stated that the 

proposed tiering system poses 

significant questions as to the nature of 

the risk assessment process. 

Specifically, commenters questioned 

listing as Tier 1 agents bacterial diseases 

that are treated with licensed 

antibiotics, that are not commonly 

spread person-to-person, and that are 

present in the environment of the 

United States; while viruses that have 

no known therapy and that pose 

extreme risk to western populations are 

absent from the Tier 1 list. The 

commenters believed that the 20 criteria 

used for evaluation of each select agent 

and toxin should be made available to 

the regulated community for review and 

assessment. We note that the 20 criteria 

referenced by the commenters were the 

ones used by the FESAP in providing 

recommendations to the Federal Select 

Agent Program. Nevertheless, we agree 

with the commenters that it is 

reasonable to publish the criteria used 

by the FESAP in providing the tiering 

recommendations to the Federal Select 

Agent Program. These criteria are: 

1. The relative ease with which a 

select agent or toxin might be acquired 

from a laboratory or commercial source; 

2. The relative ease of production of 

a select agent or toxin; 

3. The relative ease by which a select 

agent or toxin might be modified in 

order to enhance its pathogenicity, 

transmissibility, or ability to evade 

medical and non-medical 

countermeasures; 

4. The potential for easy deliberate 

dissemination; 

5. The potential for creating disease or 

illness; 

6. The relative environmental stability 

of a select agent or toxin by itself and 

how well it survives in the environment 


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in which it is formulated or 

disseminated; 

7. The amount of select agent or toxin 

necessary to induce illness; 

8. The relative ease with which a 

particular select agent or toxin might be 

disseminated or transmitted from one 

animal or person to another or into the 

environment where it could produce a 

deleterious effect upon animal, plant, or 

human health; 

9. Whether the target population has 

innate immunity to the select agent or 

toxin or whether immunity has been 

acquired from a source such as vaccines; 

10. The potential for the select agent 

or toxin to create morbidity (i.e., any 

non-fatal illness that renders partial 

dysfunction to an animal or human 

lasting weeks or months that will 

eventually resolve with medical, 

veterinary, and/or supportive care); 

11. The burden placed on the human, 

veterinary, or plant health system by the 

deliberate release of the select agent or 

toxin; 

12. The ability to detect a release of 

the select agent or toxin into the 

environment, food, water, or soil; 

13. The ability of the human and 

agricultural health authorities to 

accurately and rapidly diagnose and 

treat the disease presented by a release 

of the select agent or toxin; 

14. The existence of countermeasures 

to prevent, treat, or mitigate the 

symptoms of a disease caused by the 

release of a select agent or toxin and/or 

its spread through a population; 

15. The potential for high animal, 

plant, or human mortality rates with 

delivery of medical countermeasures; 

16. The potential for high animal, 

plant, or human mortality rates without 

delivery of medical countermeasures; 

17. The short-term economic impact 

of a single outbreak of a disease or 

release of a toxin; 

18. The human, monetary, and other 

resource costs of making an area, 

building, industrial plant, farm, or field 

safe for humans, animals or plants to 

inhabit following the release of the 

select agent or toxin; 

19. The pathogen’s ability to persist in 

the environment or to find a reservoir 

that makes its recurrence more likely; 

and 

20. The long-term health or economic 

consequences caused by a single release 

of the select agent or toxin. 

Commenters argued that if there is a 

‘‘Tier 1’’ designation of certain select 

agents and toxins, there logically should 

be a list of designated ‘‘Tier 2’’ select 

agents and toxins. We made no changes 

based on this comment. In designating 

certain select agents and toxins as ‘‘Tier 

1,’’ the Federal Select Agent Program 

considered and rejected the idea of 

designating the remaining agents as 

‘‘Tier 2’’ because the establishment of 

the Tier 1 category is in no way 

intended to imply that the agents not 

designated as Tier 1 pose a lesser risk 

to public health and safety than they 

have previously. Further, we believe 

that the establishment of more varying 

levels of risk categories would create an 

increased administrative oversight 

burden and needless complications for 

regulated entities. 

Various commenters argued that the 

following select agents should be not be 

listed as Tier 1 agents: F. tularensis, Y. 

pestis, B. mallei, B. pseudomallei, and 

B. anthracis because these bacteria are 

all readily found in the environment 

and treated effectively with antibiotics, 

such that additional security 

requirements will have little or no effect 

on biodefense. Commenters said they 

recognized that public perception must 

be taken into account, but they stated a 

belief that there is little public 

recognition of many of these bacteria as 

potential biothreat agents. Commenters 

stated that F. tularensis is not 

transmissible from one human to 

another nor does it have either the 

potential for major human health impact 

or the potential for a high mortality rate. 

Based on the FESAP recommendation 

using the criteria identified above, we 

disagree with the commenters that F. 

tularensis should not be designated as a 

Tier I select agent. Significant factors 

that we considered include the low 

infectious dose, the robust 

environmental stability, and a welldocumented history of weaponization 

associated with this agent. 

Commenters stated that B. 

pseudomallei should be not be listed as 

Tier 1 agent because B. pseudomallei is 

non-communicable from person-toperson, lacks a history of use or 

development as a successful biologic 

weapon (as compared with B. mallei, a 

highly pathogenic organism with which 

B. pseudomallei is inappropriately 

linked in the list), and has a low 

incidence of symptomatic disease 

following natural infection. The 

outcome of 99.9 percent of infections 

with B. pseudomallei is asymptomatic 

infection. Life-threatening illness occurs 

only in a few hosts with particular risk 

factors, particularly renal failure and 

diabetes. 

Based on the FESAP recommendation 

using the criteria identified above, we 

disagree with the commenters that B. 

pseudomallei should not be designated 

as a Tier I select agent. Significant 

factors in our determination include the 

fact that B. pseudomallei is as virulent 

in animal models as B. mallei, B. 

pseudomallei is not endemic in the 

United States, B. pseudomallei has a 

low infectious dose, B. pseudomallei 

possesses robust environmental 

stability, and timely diagnosis may be 

complicated due to the rareness of 

disease in the United States. In 

addressing the comment referring to the 

criteria used to remove Coccidioides, we 

note 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. We do not believe that 

this applies to B. pseudomallei. In 

addition, we note that B. pseudomallei 

is not extensively endemic in the United 

States as are Coccidioides species. 

Therefore, B. pseudomallei will be 

listed as a Tier 1 select agent and toxin. 

Commenters stated that Botulinum 

toxin should not be identified as a Tier 

1 agent because Botulinum toxin is a 

non-replicating, non-infectious 

chemical agent and should not be in the 

same category as highly contagious 

biological agents such as B. anthracis or 

un-treatable agents such as the Ebola 

virus. We made no changes based on 

these comments. We are aware that 

Botulinum toxin is a non-replicating 

and non-infectious toxin. However, the 

rule seeks to balance the regulatory 

oversight of agents and toxins that have 

the potential to pose a severe threat to 

public health and safety while 

maintaining availability of these agents 

and toxins for research and educational 

activities. Another commenter further 

argued that Botulinum neurotoxin 

quantities in excess of 500 microgram 

(mg) should be designated as Tier 1 

toxin, but quantities of less than 500 mg 

should not be regulated. One 

commenter questioned the ‘‘logic (or 

science)’’ behind this decision, 

particularly when pharmaceutical 

production facilities possessing greater 

than 500 mg will be exempt from the 

new regulations. 

We noted that the pharmaceutical 

production facilities possessing select 

agent or toxins are currently regulated 

under select agent regulations. However, 

products that are, bear, or contain listed 

select agents or toxins that are cleared, 

approved, licensed, or registered under 

any of the laws specified in Section 5(c) 

and 6(c) of the regulations are exempted 

from the requirements of the select 

agent regulations, insofar as their use is 

only for the approved purpose and 

meets the requirements of such laws. 

The exemption would only apply to the 

final product created from or containing 

the select agent or toxin. The amount of 

each toxin that could be possessed 


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without regulation by a principal 

investigator, a treating physician or 

veterinarian, or a commercial 

manufacture or distributor was 

determined on the basis of toxin 

potency and how much one could safely 

possess without constituting a potential 

threat to public safety or raising 

concerns about use as a weapon that 

would have a widespread effect. The 

level specified in the rule was 

determined after consultation with 

subject matter experts on this toxin. The 

determination that a toxin posed a 

severe public health threat was based on 

the ability for the mass distribution of 

the toxin for mass casualty purposes. 

Therefore Botulinum neurotoxin will be 

placed on the HHS Tier 1 list of select 

agents and toxins. 

Commenters stated that Ebola and 

Marburg viruses should be removed 

from Tier 1 because none of the other 

hemorrhagic fever viruses are in Tier 1, 

yet they are just as dangerous. We 

disagree with the commenters and note 

that the hemorrhagic viruses on the 

select agent list exhibit distinct 

differences in morbidity, mortality, 

transmissibility, and degree of 

pathogenicity. Therefore our 

consideration to designate a particular 

virus as Tier 1 is made on a virus-byvirus basis. Ebola virus and Marburg 

virus are designated as Tier 1 select 

agents. 

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) 

One commenter argued that 

Reconstructed 1918 Influenza virus 

should be a Tier 1 select agent since it 

is a pathogenic agent not currently 

present in any human population and 

not currently present in any natural 

environment. The commenter further 

argued this agent exhibited high 

transmissibility and high lethality and 

caused a global pandemic with massive 

mortality (≥50 million deaths; ≥3 

percent of the human population at the 

time), massive economic impact, and 

major psychological impact when last 

present in human populations. 

We did not propose to designate 

Reconstructed 1918 Influenza virus as a 

Tier 1 select agent and are making no 

changes to the HHS list of select agents 

and toxins based on this comment. 

Recent studies have increased our 

understanding of the public health risks 

associated with this agent. Current 

reports suggest that as much as 60 

percent of the population in the United 

States may have some immunity to the 

1918 Influenza virus. We also 

considered the potential availability of 

vaccines and antiviral treatments when 

considering whether to designate this 

virus as a Tier 1 select agent. 

Although we did not designate the 

Reconstructed 1918 Influenza virus as a 

Tier I select agent, we retained this virus 

as a select agent. In retaining this virus 

as a select agent we recognize that, to 

the best of our knowledge, the only 

place the Reconstructed 1918 Influenza 

virus currently resides is in laboratories. 

Unlike other influenza viruses, the most 

likely source of a Reconstructed 1918 

Influenza virus outbreak would be as a 

result of a breach or failure of a 

laboratory’s biosafety or biosecurity 

program. 

Diagnostic Laboratories and Tier 1 

Agents 

Commenters have expressed concerns 

about the ability of diagnostic 

laboratories, such as those in the LRN, 

to retain their ability to perform 

diagnostics while meeting the 

requirements for Tier 1 select agents and 

toxins. The Federal Select Agent 

Program recognizes the critical role of 

diagnostic laboratories in the early 

detection and response to outbreaks of 

disease in humans and agriculture. 

While all of the Tier 1 regulatory 

requirements will apply to laboratories 

that maintain permanent stocks of Tier 

1 select agents and toxins, laboratories 

may wish to consider maintaining their 

proficiency in detecting Tier 1 select 

agents and toxins through the use of 

excluded attenuated strains of select 

agents and toxins that meet their testing 

requirements. Examples of excluded 

attenuated strains include: B. anthracis 

strains devoid of the plasmid pX02 (e.g., 

B. anthracis Sterne, pX01+pX02-)

(effective 2–27–2003), F. tularensis 

subspecies holartica LVS (live vaccine 

strain; includes NDBR 101 lots, TSI– 

GSD lots, and ATCC 29684) (effective 2– 

27–2003), and Y. pestis strains (e.g., 

Tjiwidej S and CDC A1122) devoid of 

the 75 kb low-calcium response (Lcr) 

virulence plasmid (effective 2–27– 

2003). Possession of an excluded 

attenuated strain, so long as it has not 

been subjected to any manipulation that 

restores or enhances its virulence, 

would be excluded from the HHS and 

USDA select agent regulations. Those 

laboratories encountering a Tier 1 select 

agent or toxin in their routine work with 

diagnostic or proficiency testing, would 

still qualify for the clinical or diagnostic 

laboratory exemption found in sections 

5(a) and 6(a) of the regulations. Should 

a diagnostic laboratory wish to maintain 

a select agent identified in a diagnostic 

sample longer than the seven calendar 

days currently allowed by the select 

agent regulations, the diagnostic 

laboratory can request that HHS/CDC or 

USDA/APHIS grant additional time 

before the select agent is transferred or 

destroyed pursuant to either section 5(a) 

or section 6(a) of the regulations. 

C. Responses to Other Proposed 

Changes 

With respect to the remainder of the 

sections outlined below, the following 

changes are based on comments 

received in response to the NPRM and 

recommendations from the FESAP. We 

updated the Web address throughout 

the document as all information 

concerning the Federal Select Agent 

Program is now centralized on the 

National Select Agent Registry (NSAR) 

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

addition, HHS/CDC and USDA/APHIS 

used similar language in our final rules 

to ensure consistency between the 

regulations. 

Definitions 

Occupational Exposure 

We proposed 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 (Bloodborne pathogens). 

Commenters proposed that we not use 

the OSHA definition since the adoption 

of this definition would limit possible 

exposures to select agents only to 

bloodborne pathogens and to other 

potentially infectious materials as noted 

in that standard, but not to occupational 

exposure to aerosols of the agents in the 

select agent list. One commenter 

recommended ‘‘a definition, which 

combines the OSHA bloodborne 

pathogens standard and the definition of 

‘‘exposure incident’’ found in the 

Bloodborne Pathogen Standard and 

Exposure Incident (Laboratory) from the 

Cal/OSHA Aerosol Transmissible 

Diseases (California Code of 

Regulations, Title 8, Section 5199), to 

ensure that both non-aerosol and aerosol 

exposure events are appropriately 

addressed that would state ‘‘Exposure 

Incident: Any event which results in (1) 

an individual experiencing a specific 

eye, mouth, or other mucous membrane, 

non-intact skin, or parenteral contact 

with a select agent or toxin; or (2) an 

individual experiencing a potential 

exposure to an aerosolized select agent 

without the benefit of appropriate 

exposure controls, and the 

circumstances of the aerosol exposure 

make the transmission of a disease 

sufficiently likely that the individual 

requires further medical evaluation by a 


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Physician or other licensed health care 

professional.’’ We agree with the 

commenters and are revising the 

definition to state: ‘‘Any reasonably 

anticipated skin, eye, mucous 

membrane, parenteral contact, or 

respiratory aerosol exposure to select 

agents or toxins that may result from the 

performance of an employee’s duties.’’ 

Recombinant and Synthetic Nucleic 

Acids 

We proposed to add the definitions 

for recombinant and synthetic nucleic 

acids to the regulations. One commenter 

stated that the broad definition has 

implications in all areas of synthetic 

biology technology, including industrial 

enzymes, renewable chemicals for 

pharmaceutical and industrial 

applications, biobased products, 

personal care products, renewable 

specialty chemicals, biofuels, and 

healthcare products. The commenter 

argued that the consequences of such a 

definition could impede the growth of 

sustainable products from an emerging 

science such as synthetic biology 

technology. The commenter 

recommended that we not adopt the 

new definitions of recombinant and 

synthetic nucleic acids as put forth in 

the proposed rule because the existing 

language of the regulation is sufficient 

to cover the uses of synthetic nucleic 

acids as currently practiced; and 

furthermore, that the proposed 

definitions utilize language that was 

proposed to, but rejected by, the NIH 

Recombinant DNA Advisory Committee 

(NIH–RAC). The commenter further 

argued that if we feel compelled to 

introduce a new definition, that we 

follow the leadership of the NIH–RAC 

and promulgate a simpler definition that 

is not focused on the underlying 

mechanism of production of the nucleic 

acids. We made no changes to the 

definition based on this comment. The 

scope of our oversight is limited by the 

list of select agents and toxins and 

therefore does not extend to all 

synthetic biology. We have updated the 

organization of the definitions of 

recombinant and synthetic nucleic acids 

upon consultation with the NIH Office 

of Biotechnology Activities. The 

definitions now read as: 

• Recombinant nucleic acids. (a) 

Molecules that are constructed by 

joining nucleic acid molecules and that 

can replicate in a living cell (i.e., 

recombinant nucleic acids) or (b) 

molecules that result from the 

replication of those described in (a) 

above. 

• Synthetic nucleic acids. (a) 

Molecules that are chemically or by 

other means synthesized or amplified, 

including those that are chemically or 

otherwise modified but can base pair 

with naturally occurring nucleic acid 

molecules (i.e., synthetic nucleic acids) 

or (b) or molecules that result from the 

replication of those described in (a) 

above. 

In addition, we have separated the 

definition of recombinant and synthetic 

nucleic acids for clarity. 

Restricted Person 

We proposed to add the definitions 

for the following terms in 42 CFR 73.1, 

to clarify the criteria related to the 

identification of a restricted person: 

Adjudicated as a mental defective, 

Alien, Committed to any mental 

institution, Controlled substance, Crime 

punishable by imprisonment for a term 

exceeding 1 year, Indictment, Lawfully 

admitted for permanent residence, 

Mental institution, Restricted person, 

and Unlawful user of any controlled 

substance. Commenters stated that 

proposed definitions need to be further 

clarified and are overly restrictive or 

vague. We agree with these comments 

and are not including these definitions 

in this final rule. 

Exclusions 

We proposed to remove language 

stating that an attenuated strain of a 

select agent that had been granted an 

exclusion because it did not pose a 

severe threat to public health and safety 

would be published in the Federal 

Register. We received no comments 

regarding this proposal. However, one 

commenter requested clarification 

regarding previously established 

exclusions as currently listed on the 

NSAR at http://www.selectagent.gov/

Select%20Agents%20and%20Toxins

%20Exclusions.html. The commenter 

stated that individuals should not have 

to reapply and secure written approval 

for those attenuated strains that were 

previously recognized as excluded from 

select agent status. 

In response to this commenter, we 

note that the language posted on the 

Federal Select Agent Program Web site 

at http://www.selectagent.gov/Select

%20Agents%20and%20Toxins

%20Exclusions.html already clarifies 

that once an attenuated strain of a select 

agent (or an inactivated select toxin) is 

determined not subject to the 

requirements of select agent regulations, 

the strain or toxin will only be subject 

to regulation if there is any modification 

such that virulence is restored or 

enhanced. Therefore, individuals are 

not required to reapply and seek written 

approval for attenuated strains or 

inactive toxins that have already been 

determined by the Federal Select Agent 

Program to be excluded. 

As noted earlier, we proposed the 

removal of the South America genotypes 

of EEEV and the VEEV subtypes ID and 

IE. We have also excluded the West 

African clade of Monkeypox virus. To 

prevent confusion on how an entity 

should handle samples that have been 

determined to be within a general 

taxonomic classification (e.g., EEEV) but 

not within a particular genotype or 

subtype (e.g., NA–EEEV), we have 

maintained the current general 

taxonomic listing of HHS and overlap 

select agents as opposed to listing a 

specific strain and added an exemption 

for the strains, subtypes, or 

pathogenicity levels which are not 

considered to have the potential to pose 

a severe threat to public health and 

safety. With this change, we believe we 

have clarified that when an agent is 

initially identified by taxonomic 

classification it is subject to the select 

agent regulations until further testing is 

accomplished to exclude the particular 

agent by strain, subtype, or 

pathogenicity level. We believe it is 

important that laboratories should treat 

these select agents and toxins as though 

they must comply with this part until 

further testing can be conducted to 

verify whether the agent is indeed an 

excluded strain, subtype, or 

pathogenicity level. This change should 

not have any impact on the exemption 

for diagnostic laboratories or alter the 

process of taking in diagnostic samples 

and forwarding any potentially 

identified select agents for further 

testing. It also does not change the 

reporting criteria for when the agent is 

confirmed as a select agent. Therefore, 

we are maintaining the listing of select 

agents in 42 CFR 73.3(b) to read, 

Monkeypox virus and Eastern Equine 

Encephalitis virus, and adding the 

following criteria to be excluded in 42 

CFR 73.3(d)(5): Any South American 

genotypes of Eastern Equine 

Encephalitis virus and any West African 

Clade strains of Monkeypox virus. We 

are also amending the proposed list of 

select agents in 42 CFR 73.4(b) to read 

Venezuelan equine encephalitis virus, 

and adding the following criteria to be 

excluded in 42 CFR 73.4(d)(3): Any ID 

and IE subtypes of Venezuelan equine 

encephalitis virus. 

Toxins 

In 42 CFR 73.3(e) and 73.4(e), we 

proposed 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. We received 

comments that were supportive of this 


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proposed change and will finalize the 

change in this rule. 

We proposed to add 42 CFR 73.3(d)(4) 

which would state, ‘‘An animal 

inoculated with or exposed to an HHS 

select toxin.’’ The change allows 

animals injected with or exposed to a 

select toxin not to be considered a 

‘‘select toxin.’’ Therefore, the animals 

would not need to be housed in a 

registered space. The change eliminates 

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. We received comments 

that were supportive of this proposed 

change. 

One commenter recommended that 

we clarify that the aggregate amount in 

§ 73.3(d)(3) is per ‘‘principal 

investigator, treating physician or 

veterinarian, or commercial 

manufacturer or distributor,’’ and not 

per entity. We made no changes to the 

regulations based on this comment 

because the current regulatory language 

provides sufficient protections against 

the unrecognized accumulation of 

regulated quantities of select toxins at a 

given entity through multiple 

procurements of less than threshold 

amounts by multiple principal 

investigators within the entity. The 

same commenter recommended that we 

amend the regulatory language from 

‘‘toxin’’ to ‘‘purified toxin.’’ The 

commenter argued that since there are 

naturally occurring organisms that 

produce these toxins, unless they are 

purified they will pose only a low-level 

risk to human health. We made no 

changes to the regulation based on this 

comment since any HHS select agent or 

toxin that is in its naturally occurring 

environment, provided the select agent 

or toxin has not been intentionally 

introduced, cultivated, collected, or 

otherwise extracted from its natural 

source, is already excluded in section 

73.3. The same commenter also 

recommended that the guidance be 

clarified to state that there are some 

select toxin-producing organisms that 

are not covered under this section of the 

regulations. Although we agree that 

there are indeed toxin-producing 

organisms that are not covered under 

this section of the regulations, we made 

no changes to the regulation based on 

this comment. The regulations clearly 

state which agents are regulated. 

Guidance is also available on the select 

agent Web site (http://www.selectagent.

gov/SyntheticGenomics.html) and 

defines the select agents that are 

regulated. 

Due Diligence 

We proposed to require that an entity 

transferring a toxin in amounts which 

would otherwise be excluded from the 

provisions in 42 CFR part 73 would be 

excluded only if the transferor: (1) 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 

toxin; and (2) reports to HHS/CDC if 

they detect a known or suspected 

violation of Federal law or become 

aware of suspicious activity related to 

the toxin. The majority of our 

commenters from academic institutions 

argued that the proposed toxin due 

diligence provisions did not improve 

the safety and security of excluded 

quantities of these toxins. The 

commenters expressed concerns that if 

the toxin is being transferred to an 

individual employed by an entity which 

clearly has a bona fide research purpose, 

the laboratory providing the material 

should not have an obligation to report 

the transfer. Commenters further 

requested that the terms, ‘‘due 

diligence’’ and ‘‘legitimate need’’ be 

clarified. We made no changes to the 

regulation based on these comments. 

The proposed amended regulatory 

language to require due diligence and 

the reporting of known or suspected 

violations of Federal law in this case 

addresses concerns that an individual 

may be able to accumulate, unnoticed 

by anyone, regulated amounts of a select 

toxin by stockpiling shipments of 

unregulated amounts. We believe that 

commercial manufacturers and 

distributors already track the shipments 

of toxins as part of their quality 

management systems. We note that 

entities registered with the Federal 

Select Agent Program are already 

required to maintain records of internal 

toxin transfers. We are not defining 

either ‘‘due diligence’’ or ‘‘legitimate 

need’’ in the regulatory language 

because we believe both of these terms 

to be widely used and commonly 

understood. We would expect that, 

before transferring any amount of a 

select toxin, a reasonable person would 

satisfy themselves that the recipient had 

a legitimate need for a prophylactic, 

protective, bona fide research, or other 

peaceful purpose. We also note that 

while the transfer has to be recorded, 

the only report required by the new 

regulatory language is a report of a 

transfer believed or suspected to be a 

violation of law. 

Exemptions 

Immediate Notification of the 

Identification of a Select Agent or Toxin 

Contained in a Specimen Presented for 

Diagnosis or Verification 

We proposed to amend 42 CFR 73.5 

and 73.6 to limit the immediate 

notification requirement to only those 

select agents and toxins identified as 

Tier 1 agents and toxins because these 

agents and toxins present the greatest 

risk of deliberate misuse with the most 

significant potential for mass casualties. 

We received comments that were 

supportive of this proposed change and 

we are finalizing this requirement in 

this rule. 

Public Health Emergency 

To eliminate an unnecessary burden 

on any individual or entity responding 

to a domestic or foreign public health 

emergency, we have removed the 

provision that the individual or entity 

must complete an APHIS/CDC Form 5 

to request an exemption. Guidance on 

requesting an exemption for an 

individual or entity to respond to a 

domestic or foreign public health 

emergency may be found on the select 

agent Web site at www.selectagents.gov. 

Responsible Official 

Alternate Responsible Official 

We proposed to add language to 

clarify the role of an alternate 

Responsible Official in order to 

definitively establish that an alternate 

Responsible Official must have the full 

knowledge and authority to act for the 

Responsible Official in his/her absence. 

While commenters generally agreed, one 

commenter argued that the proposed 

changes would prohibit consultants 

from serving as an alternate Responsible 

Official. We are making no changes to 

the regulation in response to this 

comment. We first note that in the 

absence of the Responsible Official, a 

person who has been designated by the 

entity as an alternate Responsible 

Official becomes the entity’s 

Responsible Official. We believe that an 

individual acting as a consultant would 

have neither the institutional authority 

nor responsibility to allow them to serve 

as an alternate Responsible Official. 

This does not mean that an entity 

Responsible Official cannot utilize the 

services of a consultant in carrying out 

his or her duties. But the regulations 

were designed to require an entity to 

vest authority and responsibility for 

ensuring compliance with the select 


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agent regulations in one entity official 

so that the person can take action in the 

name of the entity and on behalf of the 

entity, and not merely provide advice or 

consultation. 

Commenters also recommended that a 

provision for delegation of 

responsibilities to an alternate 

Responsible Official by the Responsible 

Official should be included, even with 

the Responsible Official present, so that 

an alternate Responsible Official would 

always be acting under the direction/ 

oversight of the Responsible Official. 

Other commenters felt that it would be 

practical for the Responsible Official to 

delegate an alternate Responsible 

Official who is housed in the remote 

facility to take on the day-to-day 

responsibilities of the Responsible 

Official in that facility. We are making 

no changes to the regulations in 

response to these comments because the 

regulations already provide to the 

Responsible Official the flexibility to 

delegate the authority to perform certain 

tasks. While the regulations allow the 

Responsible Official as many assistants 

as he/she needs to ensure compliance 

with the regulations, the Responsible 

Official retains the ultimate 

responsibility for compliance. The 

regulatory provisions for the 

appointment of an alternate Responsible 

Official are in recognition of the fact 

that, as a practical matter, a single 

person cannot always be present at an 

entity. We believe that it is important 

for each entity to identify the person 

who has the responsibility for that 

entity to ensure compliance with the 

select agent regulations and this 

approach will help achieve a higher 

level of compliance than would be 

obtained from a system of shared 

responsibility. 

Duty Station 

We proposed to add a requirement 

that the Responsible Official’s regular 

place of employment or principal duty 

station must be located in close 

proximity to 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). 

As we stated in the preamble to the 

proposed rule, we believed 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. Commenters generally agreed 

with the requirement that the 

Responsible Official’s regular place of 

employment or principal duty station 

must be co-located with the physical 

location of the registered entity entered 

in section 1A of APHIS/CDC Form 1. 

One commenter recommended that we 

eliminate the requirement for the 

definition because the Responsible 

Official is frequently a high-level 

administrator at a university, such as a 

Vice President for Research, and it 

would be infeasible in many cases for 

such a Responsible Official, whose 

duties extend beyond biosecurity, to be 

physically located at a registered entity; 

it would only add a layer of 

bureaucracy, which could detract from 

a focus on security, to require a second, 

on-site Responsible Official. We made 

no changes based on this comment. As 

noted above, the Responsible Official 

should be an individual who can 

perform all of the duties required for 

that position. The regulations were 

designed to place responsibility for 

ensuring compliance with the 

regulations in one position. However, 

some commenters requested that we 

clarify the provision regarding the 

individual’s principal duty station, 

physical location, and ‘‘close proximity 

with the physical location of the 

registered entity.’’ In addition, one 

commenter requested that we explain 

how quickly the Responsible Official 

should be able to respond to onsite 

incidents in terms of turnaround time. 

Another commenter stated that they 

were not persuaded that ensuring 

compliance and a quick response to 

incidents are sufficient rationale for this 

requirement. 

In response, we are changing the 

language in section 73.9 to clearly state 

that the Responsible Official must have 

a physical (and not merely a telephonic 

or audio/visual) presence at the 

registered entity to ensure that the entity 

is in compliance with the select agent 

regulations and is able to quickly 

respond to on-site incidents involving 

select agents and toxins. We recognize 

that some entities are located on a 

campus with several registered 

laboratories situated in different 

buildings throughout the campus, and 

we believe it would be 

counterproductive to require that the 

Responsible Official be assigned to each 

physical laboratory listed on the entity’s 

registration and require a set turnaround 

time to respond quickly to on-site 

incidents. However, the Responsible 

Official should be able to respond in a 

timely manner to onsite incidents in 

accordance with the entity’s incident 

response plan. The regulations also 

contain a performance standard that the 

Responsible Official is physically 

located on the campus to ensure day-today oversight and compliance with the 

select agent regulations and to respond 

to any incident in a way that limits 

damage and ensures that select agents 

and toxins are secured and safeguarded. 

Responsible Official Training 

Requirement 

We proposed to add a specific 

requirement that all Responsible 

Officials possess the appropriate 

training or expertise to execute their 

required duties. We received multiple 

comments and concerns about fulfilling 

the provisions of this proposed 

requirement. The breadth and variety of 

training and expertise available would 

be difficult to capture in regulatory 

language. Therefore, we will continue to 

assess the performance of the 

Responsible Official based on his or her 

efficacy in implementing the select 

agent and toxin regulatory requirements 

at the entity. As such, we have accepted 

these comments and have not included 

this provision in the final rule. 

Access to Select Agents and Toxins 

Timeframe 

We proposed to decrease the 

maximum length of time in which a 

Security Risk Assessment (SRA) 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. Commenters argued that our 

proposal to shorten this time period 

would increase the work load for 

individuals, entities, the Federal Select 

Agent Program, and the Federal Bureau 

of Investigation (FBI), and would only 

add bureaucratic expense for all without 

any source of compensation to the 

investigators and institutions who are 

endeavoring to contribute 

countermeasures against biothreats. 

Another commenter stated that it would 

have a significant impact on law 

enforcement’s ability to handle the 

increased workload to conduct these 

investigations. One commenter was 

concerned that there would be delays in 

SRA approval that would negatively 

impact workload performance. 

We are making no changes to the 

regulations based on these comments. 

On January 9, 2009, the President signed 

E.O. 13486 entitled ‘‘Strengthening 

Laboratory Biosecurity in the United 

States.’’ This Executive Order 

established a working group co-chaired 

by representatives of the DOD and HHS 

Secretaries. The scope of working group 

activities pertained to the policy of the 

United States that facilities that possess 

biological select agents and toxins have 


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appropriate security and personnel 

assurance practices to protect against 

theft, misuse, or diversion to unlawful 

activity of such agents and toxins. The 

working group provided final 

recommendations through careful 

consideration of proposals from 

subgroups and comments received from 

select agent entities and the public. The 

report is available at: http:// 

orise.orau.gov/emi/scapa/files/ 

biosecurity-report.pdf. 

One of the recommendations from the 

working group to enhance security was 

to perform the SRA every three years for 

all individuals with access to select 

agents and toxins instead of the existing 

policy of performing the SRA every five 

years. We concurred with this 

recommendation. Based on input from 

the FBI, we have determined that 

conducting SRA approvals every three 

years is beneficial in increasing the 

security of registered entities. As a 

policy matter, we have been processing 

SRAs on a three-year basis since June 1, 

2011 and an increase in administrative 

burden has not been noted. We also did 

not receive any comments from the 

regulated community that they have 

experienced any additional burdens. 

Accordingly, we do not believe this 

regulatory change will result in an 

increased burden on registered entities. 

Portability 

We also proposed to amend the 

regulations in section 73.10 to add new 

provisions by which individuals may 

have access to select agents and toxins 

at entities other than the individual’s 

‘‘home’’ entity. One commenter 

suggested that the Responsible Official, 

rather than the individual as proposed, 

make the request to the HHS Secretary 

or Administrator to approve access to 

select agents or toxins at another 

registered entity for a specific period of 

time. Other commenters requested 

clarification of the process and 

suggested that limiting access to only 

one entity at the time would be 

appropriate. 

In response to these comments, we are 

amending section 73.10 to provide that 

‘‘a person with a valid approval from 

the HHS Secretary or Administrator to 

have access to select agents and toxins 

may request, through his or her 

Responsible Official, that the HHS 

Secretary or Administrator provide their 

approved access status to another 

registered individual or entity for a 

specified period of time.’’ 

One commenter wanted clarification 

that an individual would have access to 

select agents at multiple registered 

entities based on the proposed language. 

The revised language would allow 

individuals the flexibility to have access 

to select agents and toxins at entities 

other than the individual’s ‘‘home’’ 

entity. To address the commenter’s 

concern that the SRA portability process 

is unclear, additional guidance has been 

developed and is available at http:// 

www.selectagents.gov. 

Security 

Animals or Plants Accidentally or 

Intentionally Exposed to or Infected 

With a Select Agent 

One commenter was unclear 

regarding whether the security plan 

should contain procedures concerning 

animals or plants accidentally or 

intentionally exposed to or infected 

with a select toxin. We made no changes 

to the regulations based on this 

comment. As we discussed in the 

preamble for the NPRM, we are not 

requiring the security plan to address 

procedures concerning 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 and 

safety. 

Another commenter wanted to know 

if the provision was for clinical, 

veterinary, or environmental 

laboratories performing diagnostic work 

to identify a select agent in humans, 

food or environmental samples. We 

made no changes to the regulation based 

on this comment. Any select agent or 

toxin that is in its naturally occurring 

environment (e.g., sand samples that are 

naturally infected with B. anthracis or 

milk samples that contain C. burnetii) 

provided the select agent or toxin has 

not been intentionally introduced, 

cultivated, collected, or otherwise 

extracted from its natural source is 

already excluded in sections 3 and 4 of 

the select agent regulations. 

Commenters requested that we change 

the statement of ‘‘safeguarding of 

animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent’’ to read ‘‘intentionally 

exposed to, or infected with, select 

agents.’’ The commenters suggested that 

the statement would be clearer. We 

made no changes to the regulations 

based on this comment. We believe that 

animals or plants accidently exposed to 

or infected with a select agent should be 

handled as a select agent and 

safeguarded in the same manner as an 

animal or plant intentionally exposed to 

a select agent. 

Codification of Current Practices for 

Shipping, Receiving and Storage 

We proposed to codify current 

practices for shipping, receiving, and 

storage of select agents and toxins to 

ensure that regulated entities have 

consistent regulatory procedures for 

securing and monitoring the shipment, 

receipt, and storage of these items. Some 

commenters stated that codification of 

current practices for shipping, receiving, 

and storage are unnecessary and 

recommended that the provision be 

deleted. Other commenters 

recommended that we define and clarify 

the term ‘‘unexpected shipments.’’ We 

made no changes to the proposed 

regulation based on the comments since 

we believe the entity’s security plan 

should have documented processes to 

ensure select agents and toxins are 

safeguarded against theft, loss, 

intentional release or unauthorized 

access at all times, including when a 

select agent or toxin is (1) ready to be 

packaged for transportation, (2) 

packaged for shipment, or (3) received 

by a person with approval to access 

select agents and toxins. These 

procedures 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 materials. We also 

believe that the term ‘‘unexpected 

shipments’’ is self-explanatory and that 

an entity’s security plan should contain 

procedures for the handling of 

unexpected shipments (e.g., when an 

entity receives a shipment of a select 

agent that it had neither requested nor 

coordinated for, and therefore was not 

expecting). 

Information Security 

We proposed that the security plans 

of entities with select agents and toxins 

must include provisions for information 

security. Many commenters had 

questions or concerns regarding the 

additions to the security plan proposed 

in section 11(c)(9) of the select agent 

regulations. The commenters expressed 

concerns that the requirement 

represents an added regulatory burden 

and the impact of this requirement 

should be evaluated. Other commenters 

thought that persons having access to 

information about select agents should 

not be regulated as having access to the 

select agents. The commenters further 

expressed their belief that the proposed 

language is vague and lacks sufficient 

direction for securing the information. 

We agree with the commenters. The 

purpose of the requirement in question 

is to clarify section 11(c)(9)(i) of the 

regulation that requires the entity to 

have procedures in place for 

information systems control. This is an 

overarching requirement that covers 

electronic [information technology] and 

non-electronic [hardcopy] information 


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oversight by the regulated community. 

Our intent was not to regulate access to 

experimental data or the results of 

studies involving select agents and 

toxins but to regulate access to the select 

agents and toxins themselves. Therefore, 

we have revised the language in order 

to clearly indicate that the information 

security provisions in question should 

be for access to an entity’s registered 

space and records pertaining to select 

agents and toxins, as identified in 

sections 11 and 17 of this part. 

Commenters expressed concerns that 

the new information security 

requirements in section 11(c)(9)(ii) 

would require registration and security 

risk assessments for all staff managing 

records pertaining to select agent work. 

Our response is that this would depend 

on the individual’s duties. If an 

individual is able to access a select 

agent or toxin, the individual would 

need to undergo a security risk 

assessment. However, if the individual’s 

duties are limited so that he or she 

would be prevented from accessing the 

select agents or toxins, then the 

individual would not need to undergo a 

security risk assessment. 

We anticipate that these requirements 

are already being met and will merely 

require entities to document the systems 

and processes currently in place. The 

guidance documents developed in 

conjunction with this rule are, in part, 

a response to the questions and issues 

raised by the commenters. Guidance on 

information security may be found at 

www.selectagents.gov. Issues addressed 

in the guidance document include, but 

are not limited to: information 

technology security, network security, 

computer security, peripheral devices 

and data storage, physical security and 

its application to information security, 

risk management, and training. 

Inventory Verification for Select Agents 

and Toxins 

We proposed more specific minimum 

security standards for select agents or 

toxins that included inventory 

verifications for select agents and 

toxins. Commenters requested that 

section 11(e)(4)(ix) be revised to delete 

the word ‘‘all’’ and clarify that the 

inventory audits be conducted for only 

those affected Tier 1 select agents and 

toxins. We agree with the commenters 

that the intent of the proposed provision 

was limited to only those select agents 

and toxins affected by the triggering 

event. However, we reevaluated the 

proposal that would have been limited 

to only Tier 1 agents and toxins, and 

based on experience, believe that this 

provision needs to be applied to all 

select agents and toxins. Therefore, we 

have revised the final regulatory 

language to address inventory 

verification for all select agents and 

toxins, by creating a new subparagraph 

(e) in section 11 which states ‘‘(e) 

Entities must conduct complete 

inventory audits of all affected select 

agents and toxins in long-term storage 

when any of the following occur: 

(1) Upon the physical relocation of a 

collection or inventory of select agents 

or toxins for those select agents or 

toxins in the collection or inventory; 

(2) Upon the departure or arrival of a 

principal investigator for those select 

agents and toxins under the control of 

that principal investigator; or 

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

select agent or toxin, all select agents 

and toxins under the control of that 

principal investigator.’’ 

Reference 

We proposed 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 guidance 

document in March 2007 that 

supersedes this reference. We received 

no comments regarding the removing of 

this reference. 

Reporting Incidents to the FBI 

We proposed to add a requirement 

that the security plan include 

procedures for the Responsible Official 

to immediately notify the FBI of 

suspicious activity that may be criminal 

in nature and related to the entity, its 

personnel, or its select agents or toxins. 

Commenters stated that this proposal 

contradicts FBI guidance contained in 

their ‘‘Agricultural, Chemical and 

Petroleum Industry Terrorism 

Handbook’’ and creates a conflict within 

those entities that have their own 

recognized law enforcement agencies. 

Commenters requested justification for 

this change and clarification on the 

intent of the requirement. Commenters 

also argued that the proposed language 

is unclear and unnecessary. 

Specifically, commenters asked what 

constitutes a ‘‘suspicious criminal 

activity’’; what is an ‘‘entity’’; and 

whether the intent of this proposal is for 

the Responsible Official to be the 

designated individual to contact the 

FBI. We do not believe that there exists 

any conflict between the security 

requirements in section 73.11 (Security) 

of the select agent regulations and the 

guidance contained in the FBI’s 

‘‘Agricultural, Chemical and Petroleum 

Industrial Terrorism Handbook.’’ 

However, where any conflict might 

exist, the requirements of the federal 

regulations would supersede guidance. 

The intent of this requirement is to 

facilitate the involvement of 

antiterrorism resources which will 

increase the security of select agents and 

toxins. We also believe that the FBI field 

offices, which are centrally located in 

major metropolitan areas across the 

United States, can assist the entity by 

working closely with them on crime 

threats. However, we agree with the 

commenters that it may be appropriate 

that the notification of suspicious 

activity first go to the local law 

enforcement. Therefore, we have 

changed the language in section 

73.11(c)(8) to read: ‘‘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 

describe procedures for how the entity 

will notify the appropriate federal, state, 

or local law enforcement agencies of 

such activity.’’ The guidance document 

on reporting suspicious activities may 

be found at www.selectagents.gov. 

Intrusion Detection System 

We proposed more specific minimum 

security standards for select agents and 

toxins that included intrusion detection 

systems. Commenters requested 

clarification as to what was meant by 

‘‘intrusion detection system’’ (IDS) and 

asked for examples of what constitutes 

an IDS. They also requested clarification 

concerning the requirement that 

‘‘personnel monitoring the IDS must be 

capable of evaluating and interpreting 

the alarm.’’ We have made no changes 

in response to this comment. We believe 

that the terms are self-explanatory and 

these types of alarms need to be 

monitored by personnel who are 

capable of responding appropriately. 

However, we are removing the words 

‘‘prescribe and/or’’ to clarify the intent 

of the provision. We have developed 

guidance that describes IDS as a sensor 

device or devices which triggers an 

alarm when a security breach occurs 

and notifies a response force (e.g., 

police, guards, etc.) capable of 

addressing any threat that may be 

present. This guidance also provides 

examples of various types of IDS. The 

guidance document may be found at 

www.selectagents.gov. 

Submission of Security Plans 

We proposed to amend § 73.11 to 

require that the entity security plan be 

submitted for initial registration and 

renewals of registration. Commenters 

recommended that we eliminate the 

proposed requirement, and stated that 


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this requirement would delay the 

renewal process and place entities in a 

‘‘regulatory bind,’’ that the requirement 

would compromise the ‘‘need to know’’ 

status of the security plans, and that 

these documents should remain a 

protected document made available for 

review during the site visit only. We 

made no changes to the regulations 

based on these comments. Section 11 

already has a provision that ‘‘the 

security plan must be submitted upon 

request.’’ The requirement in question 

merely codifies our long-standing policy 

of requesting the security plans for 

initial registration and the renewal 

process. We also note that, in practice, 

the submission of security plans for 

initial registration and registration 

renewals has not created a delay in 

either process. 

Security for Tier 1 Select Agents and 

Toxins 

Access Controls to Tier 1 Agents 

We proposed specific minimum 

security standards for access controls to 

Tier 1 agents in section 11(4)(iii) of the 

regulations. One commenter stated that 

these provisions would be difficult for 

laboratories co-located with other 

entities. We made no changes to the 

proposed standards based on this 

comment. Based on our experience with 

over 350 entities in a ten-year period, 

we observed that registered entities have 

been successful in meeting the current 

regulatory requirements in a co-located 

situation, and we have no reason to 

believe that this will not continue. 

Back-Up Power for Tier 1 Select Agents 

and Toxins 

We proposed more specific minimum 

security standards for Tier 1 agents that 

included the provision of back-up 

power. Commenters requested 

clarification regarding whether the backup power requirement would only 

apply to registered spaces or whether it 

would include the entire entity or 

building that houses the registered 

space. Commenters recommended 

adding the phrase ‘‘for the registered 

space’’ into this section. We agree with 

the commenters and have revised the 

language accordingly. 

Another commenter stated that the 

provision should remain a 

recommendation not a requirement. 

Although we believe back-up power for 

information security networks is an 

essential component for the 

safeguarding of Tier 1 agents against 

unauthorized access, theft, loss, or 

release during power outages, further 

consideration led us to alter the nature 

of this requirement. Rather than 

focusing on power/electricity alone, we 

have clarified the requirement in order 

to address the importance of having 

comprehensive back-up procedures in 

the event of a system failure. These 

procedures may include, but are not 

limited to, provisions for back-up 

power. 

Security Enhancements for Tier 1 Select 

Agents and Toxins 

We proposed specific minimum 

security standards for Tier 1 select 

agents or toxins. Commenters requested 

guidance and a timetable of when the 

security upgrades need to be addressed. 

In this final rule, we have included a 

phase-in period for the effective date for 

certain requirements which should 

allow entities sufficient time to comply 

without causing disruption or 

termination of research or educational 

projects. As noted in the ‘‘Effective 

Dates’’ portion of this document, one 

hundred and eighty days after the 

publication of the final rule, entities 

will need to be in compliance with new 

provisions outlined in section 11 

(Security). In addition, we have 

developed guidance to assist entities 

with security enhancements for Tier 1 

agents. 

Other commenters stated that the 

proposed rule included more specific 

minimum security standards for Tier 1 

select agents and toxins and requested 

that we identify criteria for stratifying 

security requirements, making them 

risk-based and considering the type of 

work performed at the facility. The 

commenters also argued that the 

additional regulations for Tier 1 agents 

and toxins will create more 

responsibilities for the entity and 

require more resources to meet these 

requirements. While we are in general 

agreement with these concerns, we note 

that entities possessing Tier 1 agents 

and toxins are already meeting these 

requirements. In addition, we have 

developed guidance to assist entities 

with security enhancements for Tier 1 

agents, which may be found at 

www.selectagents.gov. Therefore, we are 

making no changes to the minimum 

security standards as proposed in the 

NPRM. 

Suitability Assessment for Access to 

Tier 1 Select Agents and Toxins 

We proposed specific minimum 

security standards, including personnel 

suitability assessments, for access to 

Tier 1 select agents and toxins. Many 

commenters had questions or concerns 

regarding these additional requirements, 

as described in section 11(f) of the 

proposed rule. Specific additions 

addressed by the commenters included: 

Pre-access suitability assessments, 

ongoing suitability assessments, and 

self- and peer-reporting of incidents or 

conditions that could affect an 

individual’s ability to safely have access 

to or work with Tier 1 select agents and 

toxins. Commenters generally divided 

into two groups in their response to the 

proposed additions. Some felt that the 

requirements were too vague to prove 

useful and the requirements created 

administrative burden without 

improving the overall security of Tier 1 

select agents and toxins. Others felt that 

the requirements could or would require 

entities to behave in a manner contrary 

to local laws, privacy laws, or union 

contracts. Commenters also felt that the 

proposed language, ‘‘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’’ were 

subjective standards that would be 

difficult to enforce. We agreed with the 

commenters and revised the language in 

the final rule to read that the security 

plan must contain procedures that will 

limit access to a Tier 1 select agent or 

toxin to only those individuals who are 

approved by the HHS Secretary or 

Administrator, following a security risk 

assessment by the Attorney General, 

have had an entity-conducted pre-access 

suitability assessment, and are subject to 

the entity’s procedures for ongoing 

suitability assessment. 

We anticipate that these requirements 

are already being met at many registered 

entities and will merely require those 

entities possessing a Tier 1 select agent 

or toxin to formalize and document the 

systems and processes currently in 

place. Therefore, we do not believe the 

registered entities possessing a Tier 1 

select agent or toxin will endure 

additional significant costs for 

suitability assessments. We believe that 

many of the specific concerns raised by 

commenters regarding potential 

violation of laws or union contracts 

arose as a result of the commenters’ 

examination of the FESAP November 2, 

2010 document entitled 

‘‘Recommendations Concerning the 

Select Agent Program.’’ As a matter of 

clarification, the Federal Select Agent 

Program considered the FESAP 

recommendations as well as 

recommendations from other sources 

(e.g., the National Science Advisory 

Board for Biosecurity, the National 

Research Council, and the EO 13486 

Working Group), in developing the 

proposed rule provisions addressing 

personnel suitability. While we have 

created specific guidance regarding this 


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section of the revised rule, we are 

leaving the regulations in their broadlywritten state in order to provide entities 

with flexibility in meeting these 

requirements. Given our experience 

with the select agent regulations and the 

wide variety of regulated entities those 

regulations cover, we have found this to 

be the most effective approach. The 

personnel suitability guidance 

document developed in conjunction 

with this rule is, in part, a response to 

the questions and issues raised by the 

commenters. Issues addressed in the 

guidance document include, but are not 

limited to: 

(1) Understanding the potential for 

insider threat; 

(2) Understanding the needs for 

suitability assessments; 

(3) Delineating the roles and 

responsibilities of individuals to ensure 

optimal security; 

(4) Requesting information about 

individuals in a standardized manner 

and assessing individuals in the context 

of safety and security; 

(5) Responding to reports in a 

consistent, prompt, and confidential 

manner; 

(6) Providing training for recognizing 

and reporting suspicious behavior. 

Full guidance on suitability 

assessments may be found at 

www.selectagents.gov. 

One commenter requested an 

exclusion or exemption clause for 

entities that are registered to possess 

Tier 1 select agents or toxins, but do not 

possess them. We made no changes to 

the regulations based on this comment. 

Entities that are registered to possess, 

use or transfer select agents and toxins 

must meet all of the regulatory 

requirements, regardless of whether or 

not they actually possess these 

materials. 

Security Training for Access to Tier 1 

Select Agents and Toxins 

We proposed specific minimum 

security standards, including security 

training, for those individuals who 

would have access to Tier 1 select 

agents or toxins. Commenters requested 

clarification whether training of ‘‘all 

entity employees’’ mentioned in section 

11(e)(2)(ii) meant everyone in the 

facility or those ‘‘Security Risk 

Assessment-approved employees.’’ We 

agree with the commenters and have 

revised the language in the regulations 

to clarify that the training is for 

employees with access to Tier 1 select 

agents and toxins. 

Three Barriers for Tier 1 Select Agents 

and Toxins 

We proposed specific minimum 

physical security standards for Tier 1 

select agents or toxins that included a 

requirement for three barriers protecting 

access to these materials. Commenters 

requested clarification regarding what 

was meant by ‘‘barrier’’ and asked for 

examples of what constitutes as a 

barrier. They also requested clarification 

concerning the word ‘‘delay’’ since, 

according to the commenters, the word 

does not seem to describe the needed 

function. 

We agree with the commenters that 

the word barrier needed further 

explanation and, in the definitions 

section in § 73.1, we have defined the 

term ‘‘Security barrier’’ as a physical 

structure that is designed to prevent 

entry by unauthorized persons. In 

addition, we have revised the language 

in this section to more clearly articulate 

that entities possessing Tier 1 select 

agents and toxins must have a minimum 

of three security barriers where each 

security barrier adds to the delay in 

reaching secured areas where select 

agents and toxins are used or stored. 

One of those security barriers must be 

monitored in such a way as to detect 

intentional and unintentional 

circumventing of established access 

control measures under all conditions 

(day/night, severe weather, etc.). The 

final barrier must limit access to the 

select agent or toxin to personnel 

approved by the HHS Secretary or 

Administrator, following a security risk 

assessment by the Attorney General. 

Other commenters believed that the 

proposed requirement represents an 

added expense. Although we agree that 

there are expenses associated with the 

implementation of security measures, 

we do not anticipate that significant 

additional expenditures will be 

necessary for registered entities already 

possessing Tier 1 select agents or toxins. 

We have developed guidance to assist 

entities with the security barrier 

requirement, which may be found at 

www.selectagents.gov. 

Response Time for Tier 1 Select Agents 

and Toxins 

We proposed specific minimum 

security standards, including a response 

time for security forces or local police 

that could not exceed 15 minutes from 

the time of an intrusion alarm or report 

of a security incident in section 

73.11(e)(4)(viii), for possessors of Tier 1 

select agents and toxins. Commenters 

questioned why a 15 minute response 

time was chosen. Commenters also 

inquired whether there would be any 

penalties if local law enforcement 

exceeds 15 minutes with their response 

time. In addition, commenters stated 

that the proposed definition of response 

time is unclear. One commenter 

recommended that we revise the 

provision to read ‘‘Response time for 

security forces or local police must not 

exceed 15 minutes from the time of 

alerting the designated force.’’ 

Based on the comments received, we 

have modified the language of this 

section. While retaining a 15-minute 

response time goal for security forces or 

local police, we have provided 

flexibility for entities to develop 

systems in line with the optimal 

achievable response time in their area 

by revising the language to read: ‘‘The 

entity must: (A) Determine that the 

response time for security forces or local 

police will not exceed 15 minutes or (B) 

Provide security barriers that are 

sufficient to delay unauthorized access 

until the response force arrives in order 

to safeguard the select agents and toxins 

from theft, intentional release, or 

unauthorized access. The response time 

is measured from the time of an 

intrusion alarm, or report of a security 

incident, to the arrival of the responders 

at the first security barrier.’’ 

Our selection of the 15 minute 

response time metric is based on DOD 

and DHS standards for high value assets 

(e.g., MD Number 11046 (Open Storage 

Area Standards for Collateral Classified 

Information), Department of Homeland 

Security Management Directive System 

MD) and also on our analysis of incident 

response plans provided by registered 

entities since 2003. The response time is 

measured from the time of an intrusion 

alarm, or report of a security incident, 

to the arrival of the responders at the 

first security barrier. A response is a 

force capable of interrupting a threat 

and may be unarmed guards, armed 

guards, or local law enforcement. 

Security Requirements for Variola Major 

Virus or Variola Minor Virus 

In recognition of the special public 

health risks associated with Variola 

major virus and Variola minor virus, we 

proposed to require additional physical 

security measures over and above those 

proposed for Tier 1. Commenters were 

concerned about listing the Variola 

major virus (smallpox virus) as a Tier 1 

agent, given the stringent conditions 

already in place for its handling and 

tracking. The commenters 

recommended an alternative approach 

might be to designate the smallpox virus 

as a pathogen with very special 

handling requirements, given that 

smallpox has been officially eradicated 

worldwide. 


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We made no changes to the 

regulations based on the comment. We 

believe that setting up a different special 

class of standards for one pathogen 

would needlessly increase the 

complexity of the regulatory provisions 

without any benefit of increased 

security. The requirements designated 

for Tier 1 agents were meant for those 

select agents and toxins that 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. As such, Variola 

major virus and Variola minor virus 

meet that criterion. We also note that 

Variola major virus is a special case and 

that there are additional, specific 

requirements for Variola major virus in 

addition to the Tier 1 requirements. 

These specific requirements for Variola 

major virus and Variola minor virus do 

not apply to the other Tier 1 agents. 

One commenter requested 

clarification that requirements are not 

applicable to diagnostic laboratories that 

may identify Variola major virus or 

Variola minor virus during the course of 

routine work, but would not otherwise 

‘‘possess’’ these agents. We made no 

changes to the regulations based on this 

comment. We note that the clinical and 

diagnostic laboratory exemption found 

in section 5 of the regulations, including 

all of the reporting and safeguarding 

requirements, remains in effect. 

Since the publication of the proposed 

rule, we became concerned that the 

proposed requirement for all persons 

with access to the Variola major or 

Variola minor virus to have a Top Secret 

clearance would have the unintended 

effect of preventing HHS/CDC 

researchers from being able to 

participate in collaborative work with 

international colleagues, such as 

representative of the World Health 

Organization. To address this concern, 

we have decided to modify the 

requirement to require only personnel 

with independent unescorted access to 

Variola major or Variola minor virus to 

have a Top Secret security clearance. 

The requirements that any access to 

Variola major or Variola minor would 

require approval from HHS/CDC and the 

approval of the Federal Select Agent 

Program would remain in effect. 

Biosafety Plan 

One commenter was concerned that 

specifying the ‘‘Biosafety in 

Microbiological and Biomedical 

Laboratories’’ (BMBL) (Ref 28) 

publication in the regulatory text would 

in effect incorporate the document by 

reference and therefore the BMBL 

should be published in the Federal 

Register for public comment. We made 

no changes to the regulations based on 

this comment. The BMBL has not been 

incorporated by reference. The 

regulation clearly states that an 

individual or entity should ‘‘consider’’ 

the BMBL when developing a site 

specific biosafety plan. The BMBL is 

listed in the regulations because it 

provides useful guidance for how to 

work safely with a variety of pathogens. 

It also describes standard and special 

microbiological practices, safety 

equipment, and facilities (constituting 

Biosafety Levels 1–4). It is the document 

that is generally recognized as the 

national biosafety standard in the 

United States. 

Another commenter recommended 

that we clarify features of containment 

infrastructure intended to facilitate 

biosafety of workers dealing with these 

materials. The commenter 

recommended the regulatory language 

read ‘‘The biosafety plan must contain 

sufficient information and 

documentation to describe the biosafety, 

physical and operational containment 

requirements for working with the select 

agent or toxin including any animals or 

plants intentionally or accidentally 

exposed to or infected with a select 

agent.’’ We made no changes to the 

regulations based on this comment since 

we believe the proposed language is 

clear and sufficient. 

Another commenter recommended we 

remove the statement: ‘‘The 

occupational health program may also 

be made available to individuals 

without access to Tier 1 select agents 

and toxins.’’ We agree with the 

commenter and have eliminated that 

portion of the regulatory text. 

Occupational Health Program 

We also proposed 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. 

Many commenters had questions and/or 

concerns regarding the addition of a 

requirement for an occupational health 

program. Commenters generally divided 

into two categories in their comments. 

Some commenters felt that the 

requirement was too vague to prove 

useful and that the requirement created 

an administrative burden without 

improving the overall biosafety of Tier 

1 select agents and toxins. Other 

commenters indicated that the 

requirement could or would require 

entities to behave in a manner contrary 

to Health Insurance Portability and 

Accountability Act of 1996 (HIPAA). 

Commenters also felt that a preventive 

health and post-exposure program is 

already available at registered entities 

and should not be a requirement in the 

regulations. We made no changes based 

on these comments. 

While the select agent regulations do 

not supersede HIPAA, HIPAA does not 

prevent the requirement of the 

establishment of an occupational health 

program to address biosafety concerns 

for those handling select agents and 

toxins. 

We anticipate that this requirement is 

already being met and will merely 

require those entities possessing a Tier 

1 select agent or toxin to codify and 

document the systems and processes 

currently in place. Therefore, we do not 

believe registered entities possessing a 

Tier 1 select agent or toxin will endure 

significant additional costs associated 

with an occupational health program. 

While we have created specific 

guidance regarding this section, we are 

leaving the specifics of the occupational 

health program as performance-based 

standards in order to provide entities 

with flexibility in meeting these 

requirements. We have found this to be 

the most effective approach given the 

wide variety of regulated entities these 

regulations cover. Full guidance on an 

occupational health program may be 

found at www.selectagents.gov. 

Restricted Experiments 

We proposed to add language in order 

to expand the ‘‘restricted experiment’’ 

approval requirement to include all 

experiments involving the creation of 

drug resistant select agents that are not 

known to acquire that resistance 

naturally, if such acquisition could 

compromise the control of disease 

agents in humans, veterinary medicine, 

or agriculture regardless of the method 

or technology used to create the 

resistance. Previously, the restricted 

experiment language concerned only 

those experiments involving 

recombinant nucleic acids. 

The restricted experiment definition 

currently covers the ‘‘deliberate transfer 

of a drug resistance trait to select agents 

that are not known to acquire the trait 

naturally, if such acquisition could 

compromise the use of the drug to 

control disease agents in humans, 

veterinary medicine or agriculture.’’ We 

have removed the phrase ‘‘use of the 

drug’’ and modified the language in the 

last sentence to read ‘‘deliberate transfer 

of a drug resistance trait to select agents 

that are not known to acquire the trait 

naturally, if such acquisition could 

compromise the control of disease 

agents in humans, veterinary medicine 

or agriculture.’’ We made this change 

because while the introduction of a drug 

resistance trait would normally 


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eliminate that drug as a therapeutic 

option to control the disease, there may 

be alternative drugs available to control 

the disease. Therefore, the new 

definition reads as follows: Restricted 

experiments are defined as: ‘‘(1) 

experiments that involve the deliberate 

transfer of, or selection for, a drug 

resistance trait to select agents that are 

not known to acquire the trait naturally, 

if such acquisition could compromise 

the control of disease agents in humans, 

veterinary medicine, or agriculture;’’ 

and ‘‘(2) experiments involving the 

deliberate formation of synthetic or 

recombinant nucleic acids containing 

genes for the biosynthesis of select 

toxins lethal for vertebrates at an LD[50] 

< 100 ng/kg body weight.’’ 

It should be noted that restricted 

experiments are not prohibited 

experiments. However, an entity must 

seek permission prior to the initiation of 

a restricted experiment and receive 

approval from the Administrator or HHS 

Secretary. Approval for the performance 

of a restricted experiment or the 

possession of a product of a restricted 

experiment may involve meeting 

additional safety and/or security 

requirements as prescribed by the 

Federal Select Agent Program. Many 

experiments that involve the deliberate 

transfer of a drug resistant trait do not 

meet the definition of a restricted 

experiment because the drug is not used 

to control disease in humans, veterinary 

medicine, or agriculture. The Federal 

Select Agent Program encourages 

anyone who intends to conduct a select 

agent experiment utilizing drug 

resistance markers to submit that 

experiment for review so that they can 

be advised on whether the experiment 

would be considered a restricted 

experiment and require approval prior 

to its initiation. 

One commenter stated that ‘‘denial of 

restricted experiments is an obstacle to 

the development of countermeasures 

instead of promoting real biosecurity.’’ 

We made no changes based on this 

comment. As mentioned previously, 

many experiments that involve the 

deliberate transfer of a drug resistant 

trait to a select agent do not meet the 

definition of a restricted experiment 

because the drug is not used to control 

disease in humans, veterinary medicine, 

or agriculture. The rationale for 

requiring a heightened review of 

experiments that involve introduction of 

a drug resistant trait to a select agent for 

therapeutically useful antibiotics is 

ultimately out of concern that what is 

made in the laboratory might not always 

remain in the laboratory and therefore 

present a public health or agricultural 

risk. For experimental protocols 

utilizing transient drug resistant traits, it 

should be noted that mutants possessing 

those traits can be maintained without 

removal of the trait and therefore pose 

a potential risk to public health or 

agriculture. We therefore consider these 

protocols to fall under the restricted 

experiment section of the regulations. 

Commenters also suggested aligning 

the restricted experiment language with 

the ‘‘NIH Guidelines for Research 

Involving Recombinant DNA 

Molecules’’ (NIH Guidelines) language 

that restricts and requires approval for 

experiments with pathogens involving 

drug resistance for therapeutically 

useful agents against that pathogen. We 

made no changes based on these 

comments. The definition of a restricted 

experiment is aligned with the NIH 

Guidelines and reads as ‘‘* * * select 

agents that are not known to acquire the 

resistance naturally, if such acquisition 

could compromise the control of disease 

agents in humans, veterinary medicine, 

or agriculture.’’ We have not expanded 

the definition to include the 

introduction of all drug resistant traits 

to a select agent but only to those traits 

used to control disease in humans, 

veterinary medicine, or agriculture. 

Incident Response 

One commenter argued that since the 

incident response plan must fully 

describe the entity’s response policies or 

procedures for failure of intrusion 

detection or alarm system, the Federal 

Select Agent Program should provide 

clarification as to what was meant by an 

intrusion detection system (IDS) and 

examples of what constitutes IDS. We 

have developed guidance that describes 

IDS as a sensor device or devices which 

triggers an alarm when a security breach 

occurs and notifies a response force 

(e.g., police, guards, etc.) capable of 

addressing any threat that may be 

present. This guidance also provides 

examples of various types of IDS. The 

guidance document may be found at 

www.selectagents.gov. 

One commenter recommended that 

instead of using the word ‘‘etc.’’ in 

section 14(b) they recommended that 

the section state, ‘‘* * * and 

emergencies such as fire, gas leak, 

explosion, power outage, and other 

natural and man-made events.’’ We 

agreed with the commenter and revised 

the language. 

While we did not propose any 

changes to section 73.14 (c)(6), a 

commenter recommended that the 

language regarding planning and 

coordination with local emergency 

responders be amended. Specifically, 

the commenter believed that biosafety, 

as opposed to biosecurity needs, would 

be better addressed if this provision 

read as follows: ‘‘* * * emergency 

responders, including local public 

health authorities.’’ We made no 

changes to the section based on the 

comment since the proposed language 

would limit the concept to only public 

health authorities and not agricultural 

health. Emergency responders can also 

include police, fire and rescue service, 

and emergency medical service. 

Training 

We proposed to specify that the 

Responsible Official ensure 

maintenance of training records since 

there was no particular person 

designated as the entity’s required 

record keeper, only that a training 

record must be kept. We received no 

comments regarding this proposal. 

We proposed 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. Commenters requested 

clarification concerning the required 

annual insider threat awareness 

briefings for those entities possessing a 

Tier 1 select agent or toxin as proposed 

in section 15(b) of the select agent 

regulations. The commenters asked that 

the content of these threat awareness 

briefings be made available to public 

health laboratories so that it could then 

be specifically customized for various 

regions of the country and include what 

are the minimum requirements, who the 

intended audience is, and what 

documentation will be needed to satisfy 

the requirement. 

While we have created specific 

guidance regarding this section of the 

revised regulations, the guidance does 

not take the form of a prescriptive 

program. Given our experience with the 

select agent regulations and the wide 

variety of entities those regulations 

cover, we have found a broader 

approach to be most effective. The 

guidance documents developed in 

conjunction with this rule are, in part, 

a response to the questions and issues 

raised by the commenters. The 

document regarding annual insider 

threat awareness briefings includes a 

designated person to manage the 

assessment of laboratory personnel, 

laboratorian involvement in threat 

mitigation, and behaviors of concern as 

specific examples of best practices that 

we believe entities would be well served 

in adopting. Full guidance on this and 

other issues may be found at 

www.selectagents.gov. 


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One commenter proposed that the 

requirements for incident response 

training should remain as currently 

written to only include safety incident 

training via annual blood-borne 

pathogens, general safety, biological 

hygiene, chemical hygiene, and lab 

specific select agent training. We made 

no changes to the proposed requirement 

based on this comment because we 

believe that incident response training 

needs to be expanded so that personnel 

are trained in how to safeguard select 

agents and toxins during natural 

emergencies and man-made disasters. 

Commenters requested clarification 

that refresher training would only be 

mandated when substantive changes are 

made to the plans including what level 

of retraining would be required and 

whether retraining would only be 

required for those areas of the plan that 

have been amended. We made no 

changes to the proposed requirements 

based on these comments. We believe 

that the regulatory language clearly 

states that training will need to be 

provided when significant processes are 

changed in the plan and that training 

will need to be provided to those 

individuals who are affected by these 

changes in the plan. 

One commenter recommended that 

we consider the staff time it will take for 

visitor training. We made no changes to 

the proposed requirement based on this 

comment. First, we believe that it is 

very important that visitors receive the 

appropriate incidence response and 

security awareness training to protect 

their personal safety while in registered 

areas. We do not believe that the staff 

time needed to fulfill this requirement 

will cause a significant increase in time 

and effort when integrated into the 

current visitor training program. 

One commenter requested 

clarification on the refresher training of 

escorted personnel and visitors because 

the commenter believed that refresher 

training is only required once a year, but 

does not happen with visitors or 

escorted personnel. We agreed with the 

commenter and have revised the 

language to read: ‘‘Refresher training 

must be provided annually for 

individuals with access approval from 

the HHS Secretary or Administrator or 

at such time as the registered individual 

or entity significantly amends its 

security, incident response, or biosafety 

plans.’’ 

Transfers 

We proposed to clarify when 

‘‘transportation in commerce’’ begins 

and ends to better allow registered 

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. One 

commenter stated that the security of 

the package between steps (2) packaged 

for shipment and (3) received and 

handled by a person with approval to 

access select agents and toxins should 

be the sole responsibility of the courier. 

We made no changes to the language 

based on this comment. As stated in the 

preamble to the proposed rule, 

‘‘transportation in commerce’’ begins 

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

packaged for shipment and ready for 

receipt by a courier 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. 

Commenters believed that the new 

provision outlined in section 16(f) 

meant that all transfers must be made 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. We agreed with 

the commenters and revised the 

language to state that after authorization 

is provided by USDA/APHIS or HHS/ 

CDC, the packaging of the select agent(s) 

and toxin(s) is performed by an 

individual approved by the HHS 

Secretary or Administrator to have 

access to select agents and toxins and is 

in compliance with all applicable laws 

concerning packaging. 

Records 

We proposed 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). 

Commenters argued that counting 

individual vials of replicating biological 

agents is costly, burdensome, and a 

major source of frustration for 

investigators. They further claimed that 

there is widespread concern that both 

counting vials and measuring volumes 

of individual vials are not effective 

means of increasing security and 

wondered if there was another way to 

account for inventory. Other 

commenters noted that animals infected 

with a select agent are part of ongoing 

experimentation and are thus part of 

working stocks rather than current 

inventory and requested clarification on 

whether or not the term ‘‘animal’’ also 

included ‘‘arthropods.’’ 

We are making no changes to the 

regulations based on these comments. 

While we are aware of the burden 

resulting from the requirement to 

maintain an accurate and current 

inventory of each select agent and toxin 

held in long-term storage, we believe 

this is an essential element to establish 

security of select agents or toxins. We 

recognize that it may still be possible for 

an insider to steal a sample of an agent 

either from working stock or from an 

inventory without being detected. 

However, if an entity has a robust 

inventory management system, such 

incidents have a better chance of being 

detected. To assist registered entities in 

meeting the requirements for accurate 

inventories of materials in long term 

storage, we have developed guidance 

that may be found at 

www.selectagents.gov. 

It should be noted that while the 

volume measurements the commenter 

references are required for inventories of 

select toxins, they are not required in 

the case of inventory of select agents 

held in long-term storage due, in part, 

to the points raised by the commenter. 

However, we disagree with the 

commenter’s assessment that measuring 

volume in the case of select toxins and 

counting vials in general, as part of 

required inventory tracking of both 

select agents and toxins for registered 

entities, is not necessary. 

We recognize that there has been 

some confusion between those infected 

animals (including arthropods) and 

plants considered to be ‘‘working stock’’ 

and those considered to be ‘‘inventory 

held in long term storage.’’ To that end, 

we have developed specific guidance 

that will enable entities to better 

differentiate between these two 

categories. This guidance is available at 

www.selectagents.gov. 

In order to clarify our intent regarding 

‘‘working stock’’ and ‘‘inventory held in 

long term storage,’’ as it relates to 

infected animals and plants, we are 

revising paragraph (a)(2) in section 17 of 

the select agent regulations to require an 

accurate, current accounting of any 

animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent (including number and 

species, location, and appropriate 

disposition) instead of an accurate, 

current inventory of those animals or 

plants. 

One commenter had concerns about 

tracking nucleic acids for laboratories, 

which generate bacterial mutants and 

perform reverse genetics. The 

commenter believed that this would be 


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incredibly time consuming, overly 

burdensome, and of no value. The 

commenter argued that the theft of viral 

genetic elements would be less useful to 

a person without scientific expertise 

and unnecessary for the individual with 

the skills. 

We made no changes to the 

regulations based on this comment. It 

should be noted that not all 

recombinant material is regulated. The 

scenarios described by this commenter 

would not involve regulated nucleic 

acids. For example, bacterial genomes 

and viral genomes not determined to be 

infectious are not subject to these 

regulations. Additional guidance on this 

topic is available at 

www.selectagents.gov. 

Administrative Review 

We proposed 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 

or access approval. Specifically, we 

proposed 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. In addition, we 

proposed 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. We received comments 

supporting these proposed changes. 

Guidance Documents 

In the proposed rule, we specifically 

requested comment from the regulated 

community and any other interested 

persons on the need for and desirability 

of guidance documents that would serve 

to assist regulated entities in meeting 

the requirements of regulations. We 

were particularly interested in public 

comment regarding Web sites, articles, 

or other sources that may be useful in 

developing such guidance documents. 

We received a number of comments on 

the issue of guidance which are 

discussed below. As these comments 

pertain to the development of guidance 

documents and not to the regulations 

themselves, we have made no regulatory 

changes as a result. Guidance 

documents may be found at 

www.selectagents.gov. 

Commenters stated that further 

sources of information, apart from 

interaction with Federal Select Agent 

Program inspectors, should be made 

available to assist regulated entities in 

implementing the additional 

requirements. Other commenters urged 

that we develop guidance as a 

collaborative effort with a variety of 

subject matter experts both inside and 

outside the government. 

We agreed with these comments and 

consulted with a wide variety of 

contributors including HHS and USDA 

subject matter experts, a National 

Science Advisory Board for Biosecurity 

report entitled ‘‘Enhancing Personnel 

Reliability among Individuals with 

Access to Select Agents’’ (Ref 24), the 

National Academies Committee on 

Laboratory Security and Personnel 

Reliability Assurance Systems for 

Laboratories Conducting Research on 

Biological Select Agents and Toxins 

report entitled ‘‘Responsible Research 

with Biological Select Agents and 

Toxins’’ (Ref 25), the Report from the 

Executive Order 13486 Working Group 

on Strengthening Laboratory Security in 

the United States (Ref 26), and a report 

from the Defense Science Board Task 

Force on Department of Defense 

Biological Safety and Security Program 

(Ref 27). 

There exist a variety of ways for 

regulated entities to obtain information 

from the Federal Select Agent Program. 

HHS/CDC and USDA/APHIS may be 

contacted via email at lrsat@cdc.gov or 

Agricultural.Select.Agent.Program@

aphis.usda.gov, respectively. Guidance 

is also available at 

www.selectagents.gov. The Federal 

Select Agent Program issues periodic 

email updates, which are sent to 

Responsible Officials and alternate 

Responsible Officials at all registered 

entities. We also hold workshops on 

various topics of concern to the 

regulated community. Examples of past 

workshops have discussed personnel 

reliability programs, security plans, 

preparing a registration package, and the 

inspection process. 

Miscellaneous 

Coordination Between USDA/APHIS 

and HHS/CDC 

One commenter expressed general 

support for the harmonization of APHIS 

and CDC select agent regulations. The 

commenter stated that such 

coordination could be further achieved 

via joint inspections of registered 

entities. We are making no changes as 

a result of this comment since it is 

outside the scope of this rulemaking. 

The commenter further stated that 

language and definitions used in the 

USDA/APHIS and HHS/CDC regulations 

should be consistent, citing HHS/CDC’s 

use of the term ‘‘biosafety’’ in 42 CFR 

73.12 as compared to the term 

‘‘biocontainment’’ found in USDA/ 

APHIS’s regulations in 7 CFR 331.12. 

Since the Federal Select Agent 

Program is jointly administered by 

USDA/APHIS and HHS/CDC, we make 

every effort to achieve congruence 

between our various regulations. In 

certain cases, as a result of the 

differences between plant, animal and 

human select agents and toxins, the 

terminology employed must necessarily 

differ. The term ‘‘biocontainment’’ is 

found in the USDA/APHIS regulations 

in 7 CFR 331.12 relating to Plant 

Protection and Quarantine (PPQ) select 

agents and toxins while the term 

‘‘biosafety’’ is found in the USDA/ 

APHIS regulations in 9 CFR 121.12 

relating to Veterinary Services (VS) 

select agents and toxins. ‘‘Biosafety’’ is 

the accurate term to describe procedures 

relating to humans or animals. However, 

the term ‘‘biocontainment’’ is more 

appropriate for describing procedures 

necessary to contain plant pathogens. 

Animals or Plants Exposed to or 

Infected With Select Agents or Toxins 

We proposed to require that security, 

biosafety, and incident response plans 

include provisions to address the 

safeguarding of animals or plants 

accidentally or intentionally exposed to 

or infected with select agents against 

unauthorized access, theft, loss or 

release. Commenters requested 

clarification about whether this 

requirement would be limited to 

experimental plants and animals that 

are possessed by and controlled by the 

registered entity. We made no changes 

to the requirement based on these 

comments. An entity’s security, 

biosafety, and incident response plans 

should address any plants or animals 

within the entity that may be exposed 

to a select agent, regardless of whether 

or not the exposure was intentional or 

accidental. 

Another commenter requested 

clarification on whether the term 

‘‘animal’’ included arthropods. We 

made no changes based on this 

comment as the term ‘‘animal’’ does 

include arthropods. 

Cost 

Commenters requested that we 

consider the indirect consequences of 

continuing to include agents and toxins 

on the select agent list, the negative 

effect of the proposed rule changes on 

the potential workforce for select agent 

research, and the possibility that 

additional regulations concerning Tier 1 

select agents and toxins will mandate 

more federal oversight and institutional 


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compliance requirements, resulting in 

increased costs to taxpayers both 

directly and indirectly through reduced 

research efficiency. Commenters 

requested that a full financial and 

scientific impact of these added 

requirements be carefully assessed prior 

to implementation, especially the 

increased costs to academic institutions 

with no associated funding, and the 

increased burden on investigators 

already having difficulty finding time 

for research and experimentation. The 

commenters also stated that the timeline 

for implementation of the new 

requirements should be considered and 

disclosed to affected entities. 

A cornerstone of the Federal Select 

Agent Program is to establish and 

enforce safety and security measures to 

prevent access to select agents and 

toxins for use in domestic or 

international terrorism or for any other 

criminal purpose. An equally important 

function of the Federal Select Agent 

Program is to allow for the appropriate 

availability of biological agents and 

toxins for research, education, and other 

legitimate purposes. To achieve both 

requires the balancing of the need for 

continuing biological research with 

requiring a level of safety and security 

commensurate with the risks posed by 

these biological agents and toxins. We 

understand that safety and security 

requirements cost money and that 

money in the area of biological research 

is often a scarce commodity. However, 

we are also aware that a lack of adequate 

safety and security requirements could 

result in damages measured both in 

dollars and in human lives. It is our 

determination, based on the information 

available to us, that the additional 

requirements would not constitute a 

significant economic or recordkeeping 

burden on the regulated entities. We 

also believe that in many cases these 

regulations serve to codify systems and 

procedures already in use by a majority 

of regulated entities. 

To achieve regulatory flexibility, we 

have included a phase-in period for the 

effective date for certain requirements of 

the revised regulations which should 

allow entities to comply without 

causing disruption or termination of 

research or educational projects. As 

noted in the ‘‘Effective Dates’’ portion of 

this document, sixty (60) days from the 

publication of the final rule, entities 

will need to be in compliance with 

sections 1–10, 13, 16, and 20. One 

hundred and eighty days after the 

publication of the final rule, entities 

will need to be in compliance with 

sections 11 (Security), 12 (Biosafety), 14 

(Incident response), and 15 (Training). 

Request for a Letter of Interpretation 

Policy 

One commenter suggested that the 

Federal Select Agent Program should 

augment guidance documents with a 

letter of interpretation policy. 

Specifically, the commenter 

recommended that select agent 

registrants should be able to submit 

written requests detailing a compliance 

issue and receive back a written letter of 

interpretation from the Federal Select 

Agent Program in a similar manner as 

employers can submit requests for 

interpretation to the Department of 

Labor Occupational Safety and Health 

Administration. We are making no 

changes to the select agent regulations 

based on this comment because it is 

outside the scope of this rule. 

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). Executive Order 13563 

emphasizes the importance of 

quantifying both costs and benefits, of 

reducing costs, of harmonizing rules, 

and of promoting flexibility. 

Under Executive Order 12866, HHS 

must determine whether a regulatory 

action is ‘‘significant.’’ A ‘‘significant 

regulatory action’’ under Executive 

Order 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 is protected, 

this rule has been determined to be 

‘‘significant’’ under Executive Order 

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 Executive Order 12866, 

and a final regulatory flexibility analysis 

(See Section III.B. of this Preamble) that 

examines the potential economic effects 

of this rule on small entities, as required 

by the Regulatory Flexibility Act. The 

economic analysis is summarized 

below. Copies of the full analysis are 

available on www.regulations.gov, 

Docket CDC–2012–0012, at www.select 

agents.gov or by contacting the person 

listed under FOR FURTHER INFORMATION

CONTACT. 

Summary of the Regulatory Impact 

Analysis 

The Public Health Security and 

Bioterrorism Preparedness and 

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

provides for the regulation of certain 

biological agents and toxins that have 

the potential to pose a severe threat to 

human, animal, or plant health, or to 

animal or plant products. The Animal 

and Plant Health Inspection Service 

(APHIS) and the Centers for Disease 

Control and Prevention (CDC) have 

primary responsibility for implementing 

the provisions of the Act within the 

Department of Agriculture and the 

Department of Health and Human 

Services, 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. USDA/APHIS 

and HHS/CDC coordinate regulatory 

activities for overlap select agents and 

toxins that have been determined to 

pose a severe threat to human and 

animal health or animal products. 

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

require a biennial review and 

republication of the select agent and 

toxin list, with revisions as appropriate 

in accordance with this law. These final 

rules will implement the 

recommendations of the third biennial 

review, and incorporate risk-based 

tiering of the select agent and toxin lists, 

as required by Executive Order 13546, 

‘‘Optimizing the Security of Biological 

Select Agents and Toxins in the United 

States.’’ In addition, the APHIS and CDC 

final rules will codify several 

amendments to the regulations, 

including the addition of definitions 

and clarification of language concerning 

security, training, biosafety/ 


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biocontainment, and incident response. 

These changes will improve the 

applicability and effectiveness of the 

select agent regulations and provide for 

enhanced program oversight. 

Based on information obtained 

through site-specific inspections, we 

believe most registered entities already 

have in place many of the information 

security requirements set forth in the 

final rules, and compliance costs of the 

rules are therefore expected to be 

minimal. Entities more likely to be 

affected will be laboratories and other 

institutions conducting research and 

related activities that involve the use of 

select agents and toxins categorized as 

Tier 1. These entities will be required to 

conduct a pre-access suitability 

assessment of individuals with access to 

a Tier 1 select agent or toxin, as well as 

enroll these individuals in an 

occupational health program. 

The rules would reduce the period 

that FBI background checks are valid 

from five to three years. This increased 

frequency would effectively increase the 

cost of background checks by 67 

percent. Based on the current number of 

individuals required to have the 

background checks, we estimate that the 

present value of these government-borne 

costs over five years will increase by 

$1.96 million across all registered 

entities. The annual increase in costs 

will total about $432,000. 

While we expect few if any of the 

registered entities to incur significant 

compliance costs, required 

documentation of measures already 

regularly performed with respect to 

biocontainment/biosafety, incident 

response, information security, and 

ongoing suitability assessment may 

require additional time of personnel. We 

estimate additional recurring costs 

related to information security, such as 

for software updates, could total about 

$2 million per year, or about $5,500 per 

entity, in the unlikely event that none 

of the entities already uses equivalent 

information security measures. As 

noted, many of these costs are already 

currently borne by entities in their 

conduct of generally recognized best 

practices. For entities possessing a Tier 

1 agent or toxin, the costs of pre-access 

suitability assessments and 

occupational health programs are 

estimated to total between $2.8 million 

and $4.4 million, or between about 

$9,600 and $15,100 per entity, on 

average. Again, actual costs incurred are 

unlikely to reach these maximum cost 

ranges; we expect that many of the 

entities with a Tier 1 agent or toxin 

already conduct assessments and have 

health programs similar or equivalent to 

those required by the final rules. 

The benefits of strengthened 

safeguards against the unintentional or 

deliberate release of a select agent or 

toxin greatly exceed compliance costs of 

the rules. As an example of losses that 

can occur, the October 2001 anthrax 

attacks caused 5 fatalities and 17 

illnesses, disrupted business and 

government activities (including $2 

billion in lost revenues for the Postal 

Service), and required more than $23 

million to decontaminate one Senate 

office building and $3 billion to 

decontaminate postal facilities and 

procure mail-sanitizing equipment. 

Deliberate introduction greatly increases 

the probability of a select agent 

becoming established and causing wideranging and devastating impacts to the 

economy, other disruptions to society, 

and diminished confidence in public 

and private institutions. 

The amended regulations will 

enhance the protection of human, 

animal, and plant health and safety. The 

final rules will reduce likelihood of the 

accidental or intentional release of a 

select agent or toxin. Benefits of the 

rules will derive from the greater 

probability that a release will be 

prevented from occurring. 

SUMMARY OF THE ESTIMATED MAXIMUM ADDITIONAL COSTS ATTRIBUTABLE TO THE FINAL RULES FOR THE FEDERAL

GOVERNMENT AND AFFECTED ENTITIES 1

Unit cost Number of units Total additional cost 

Added Annual Cost for the Federal Government 

Increased frequency of FBI/CJIS background 

checks.

$240 per person ..................... 13,488 approved SRAs; 

checks valid for three years.

$432,000 per year 2. 

Added Recurring Costs for Affected Entities 3

Submission of Security Plan ............................. $4.95 per submission ............. Estimated 130 annual renewals.$643.50 per year. 

Information Security 4

network connectivity monitoring 

(encryption software).

$24–$37 per license ............... 365 registered entities ............ $8,760–$13,505 per licensing 

period. 

network connectivity monitoring (firewall 

software).

$79–$199 per license ............. 365 registered entities ............ $28,835–$72,635 per licensing period. 

malware software 4 (intrusion detection) ... $15 per computer ................... 365 registered entities ............ $5,475 per software update. 

malware software (antivirus) ..................... $80 per user per year ............ 13,488 approved SRAs .......... $1,079,040 per year. 

system software updates (dedicated time 

for IT Specialist).

$2,400 per year ...................... 365 registered entities ............ $876,000 per year. 

Total 5 ................................................. approximately $2 million annually, or on average about $5,500 per registered entity. 

Added Costs for Entities that have a Tier 1 Select Agent or Toxin 3,6

Pre-suitability Assessment ................................ $100–$120 per person ........... 13,488 approved SRAs .......... $1.35–1.62 million. 

Occupational Health Program .......................... $107–$204 per person ........... 13,488 approved SRAs .......... $1.44–2.75 million. 


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SUMMARY OF THE ESTIMATED MAXIMUM ADDITIONAL COSTS ATTRIBUTABLE TO THE FINAL RULES FOR THE FEDERAL

GOVERNMENT AND AFFECTED ENTITIES 1—Continued 

Unit cost Number of units Total additional cost 

Total 7 ................................................. approximately $2.8 million–$4.4 million, or on average about $9,600–$15,100 per entity with a 

Tier 1 agent or toxin 

1The costs for registered entities summarized in this table are the estimated maximum additional expenditures that would be incurred, if none 

of the entities currently meets any of the additional security requirements set forth in the final rules. In addition, there will be the opportunity cost 

of additional time required to modify biosecurity and incident response plans and to conduct audits. Entities will be required to conduct complete 

inventory audits of all select agents and toxins in long-term storage upon the physical relocation of a collection or inventory of select agents or 

toxins, upon the departure or arrival of a principal investigator for those select agents or toxins, or in the event of a theft or loss of a select agent 

or toxin. Time costs are noted qualitatively in the Benefits and Costs section of this analysis. 2The annual additional cost estimate assumes a uniform distribution of the 13,488 background checks over three years. 

3Based on site inspections, many of the entities currently have provisions in place similar or equivalent to those required. 

4Several of the recurring costs are associated with technological updating of information security, such as firewall and malware software updates. Estimated costs across all entities are uncertain as information is unavailable regarding the number of computers per affected entity. The 

estimates assume a single computer per entity is used for covered work. 5Assumes costs of licensing and software updates are incurred annually. 

6Estimated costs are likely overstated as not all SRA-approved individuals will have access to Tier 1 select agents and toxins. 

7Average cost per entity is based on 292 entities that are registered to possess a Tier 1 agent or toxin. 

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 have prepared an 

economic analysis for this rule. The 

economic analysis provides a costbenefit analysis, as required by 

Executive Order 12866, and a final 

regulatory flexibility analysis that 

examines the potential economic effects 

of this rule on small entities, as required 

by the Regulatory Flexibility Act. Based 

on the economic analysis, which is 

available at www.selectagents.gov, we 

do not expect the rule to have a 

significant economic impact on small 

entities. In the absence of significant 

economic impacts, we have not 

identified alternatives that would 

minimize such impacts. 

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 final rule 

will be reviewed by the Office of 

Management and Budget (OMB) as a 

revision to existing OMB Control 

Number 0920–0576, expiration 10/31/ 

2014. 

USDA/APHIS and HHS/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. 

USDA/APHIS and HHS/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. 

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.) 

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 2,660 

§ 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 


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Section Form name Number of 

respondents 

Number of 

responses per 

respondent 

Average 

burden per 

response 

(in hours) 

Total burden 

hours 

§ 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 

may be obtained by calling the CDC 

Reports Clearance Officer at (404) 639– 

5960 or sending an email to 

omb@cdc.gov. HHS/CDC is requesting 

continued OMB approval to collect this 

information through the use of five 

updated forms. These forms are: (1) 

Application for Registration, (2) 

Transfer of Select Agent or Toxin Form, 

(3) Facility Notification of Theft, Loss, 

or Release Form, (4) Clinical and 

Diagnostic Laboratory Reporting Form, 

and (5) Request for Exemption. 

D. Executive Order 12988: Civil Justice 

Reform 

This rule has been reviewed under 

Executive Order 12988, Civil Justice 

Reform. Once the final rule is in effect: 

(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 

Executive Order 13132, Federalism. The 

review reveals that this regulation will 

not have substantial and direct effects 

on Tribal governments and will not 

have significant Tribal implications. 

F. Plain Writing Act of 2010 

Under Public Law 111–274 (October 

13, 2010), HHS has attempted to use 

plain language in promulgating the rule 

consistent with the 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 fever-associated 

arenavirus from southern Africa. 

PLoS 2009 May; 5(5):e1000455. 

Epub 2009 May 29. Available at 

www.plospathogens.org. 

3. World Health Organization. Summary 

of probable SARS cases with onset 

of illness from 1 November 2002 to 

31 July 2003 [monograph on the 

Internet]. 2003 Dec 31 [cited 2004 

Aug 26]. Available from http:// 

www.who.int/csr/sars/country/ 

table2004_04_21/en/ 

4. World Health Organization. SARS 

case in laboratory worker in 

Taiwan, China [monograph on the 

Internet]. 2003 Dec 17 [cited 2004 

Aug 26]. Available from http:// 

www.who.int/mediacentre/releases/ 

2003/np26/en/ 

5. World Health Organization. China 

confirms SARS infection in another 

previously reported case: summary 

of cases to date—Update 5 

[monograph on the Internet]. 2004 

Apr 30 [cited 2004 Aug 26]. 

Available from http://www.who.int/ 

csr/don/2004_04_30/en/ 

6. World Health Organization. China’s 

latest SARS outbreak has been 

contained, but biosafety concerns 

remain—Update 7 [monograph on 

the Internet]. 2004 May 18. 

Available from http://www.who.int/ 

csr/don/2004_05_18a/en/ 

index.html 

7. Liang, G., Chen, Q., Xu, J., Liu, Y., 

Lim, W., Peiris, J. S., Anderson, L. 

J., Ruan, L., Li, H., Kan, B., et al. 

Laboratory diagnosis of four recent 

sporadic cases of communityacquired SARS, Guangdong 

Province, China. (2004) Emerg. 

Infect. Dis. 10, 1774–1781. 

8. Sayeed et al. Epsilon-toxin is required 

for most Clostridium perfringens 

type D vegetative culture 

supernatants to cause lethality in 

the mouse intravenous injection 

model. Infect Immun. 2005 

Nov;73(ll):7413–21 

9. Favreau P, Krimm I, Le Gall F, 

Bobenrieth MJ, Lamthanh H, Bouet 

F, Servent D, Molgo J, Me ́nez A, 

Letourneux Y, Lancelin JM. 

Biochemical Characterization and 

Nuclear Magnetic Resonance 

Structure of Novel a-Conotoxins 

Isolated from the Venom of Conus 

consors. Biochemistry. 1999 May 

11;38(19):6317–26 

10. Groebe DR, Dumm JM, Levitan ES, 

Abramson SN. alpha-Conotoxins 

selectively inhibit one of the two 

acetylcholine binding sites of 

nicotinic receptors. Mol Pharmacol. 

1995 Jul;48(1):105–11. 

11. Groebe DR, Gray WR, Abramson SN. 

Determinants Involved in the 

Affinity of a -Conotoxins GI and SI 

for the Muscle Subtype of Nicotinic 

Acetylcholine Receptors. 

Biochemistry. 1997 May 

27;36(21):6469–74. 

12. Liu L, Chew G, Hawrot E, Chi C, 

Wang C. Two potent alpha3/5 

conotoxins from piscivorous Conus 

achatinus. Acta Biochim Biophys 

Sin (Shanghai). 2007 Jun; 

39(6):438–44. 

13. Acetylcholine Receptor BindingCharacteristics of Snake and Cone 

Snail Venom Postsynaptic 

Neurotoxins: Further Studies with a 

Non-radiological Assay. Bradley G. 

Stiles. Toxicon. 1993 Jul;31(7):825– 

34. 

14. Galgiani, J.N. 1999. 

Coccidiomycosis: a regional disease 

of national importance. Ann Intern. 

Med. 130:293–298. 

15. Chen N., et al. 2005. Virulence 

differences between monkeypox 

virus isolates from West Africa and 

the Congo basin. Virology 340:46– 

63. 

16. Hutson C. L., et al. 2009. A prairie 

dog animal model of systemic 

orthopoxvirus disease using West 

African and Congo Basin strains of 

monkeypox virus. J. Gen. Virol. 

90:323–333. 

17. Saijo M., et al. 2009. Virulence and 

pathophysiology of the Congo Basin 

and West African strains of 

monkeypox virus in non-human 

primates. J. Gen. Virol. 90:2266– 

2271. 

18. Sbrana E., Xiao S. Y., Newman P. C., 

Tesh R. B. 2007. Comparative 

pathology of North American and 

central African strains of 

monkeypox virus in a ground 

squirrel model of the disease. Am. 

J. Trop. Med. Hyg. 76:155–164. 

19. Likos AM, Sammons SA, Olson VA, 

Frace AM, Li Y, Olsen-Rasmussen 

M, Davidson W, Galloway R, 


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Khristova ML, Reynolds MG, Zhao 

H, Carroll DS, Curns A, Formenty P, 

Esposito JJ, Regnery RL, Damon IK. 

A tale of two clades: monkeypox 

viruses. J Gen Virol. 2005 Oct; 86(Pt 

10):2661–72. 

20. Azad and Radulovic, 2003: Azad AF, 

Radulovic S Pathogenic rickettsiae 

as bioterrorism agents. Ann N Y 

Acad Sci. 2003; 990: 734—738. 

21. Gresı ́kova ́ M, Kaluzova ́ M, 1997. 

Biology of tick-borne encephalitis 

virus. Acta Virol. Apr;41(2):115–24. 

22. Ecker M, Allison SL, Meixner T, 

Heinz FX, 1999. Sequence analysis 

and genetic classification of tickborne encephalitis viruses from 

Europe and Asia. J Gen Virol. Jan;80 

(Pt 1):179–85. 

23. Raoult D, Houpikian P, Tissot DH, 

Riss JM, Arditi-Djiane J, Brouqui P. 

Treatment of Q fever endocarditis: 

comparison of 2 regimens 

containing doxycycline and 

ofloxacin or hydroxychloroquine. 

Arch Intern Med. 1999;159(2):167– 

73 

24. National Science Advisory Board for 

Biosecurity report: ‘‘Enhancing 

Personnel Reliability among 

Individuals with Access to Select 

Agents’’ (http://oba.od.nih.gov/bio

security/meetings/200905T/NSABB

%20Final%20Report%20on

%20PR%205-29-09.pdf). 

25. Responsible Research with 

Biological Select Agents and 

Toxins, Committee on Laboratory 

Security and Personnel Reliability 

Assurance Systems for Laboratories 

Conducting Research on Biological 

Select Agents and Toxins, National 

Research Council of the National 

Academies (http://www8.national

academies.org/cp/projectview.aspx?

key=49097). 

26. Report of the Working Group on 

Strengthening the Biosecurity of the 

United States, Executive Order 

13486 Working Group (http://

edocket.access.gpo.gov/2009/pdf/ 

E9-818.pdf). 

27. Defense Science Board Task Force 

on Department of Defense 

Biological Safety and Security 

Program (http://www.acq.osd.mil/

dsb/reports/ADA499977.pdf). 

28. Biosafety in Microbiological and 

Biomedical Laboratories (http://

www.cdc.gov/biosafety/

publications/bmbl5/index.htm). 

List of Subjects in 42 CFR Part 73 

Biologics, Packaging and containers, 

Penalties, Reporting and recordkeeping 

requirements, Transportation. 

Dated: September 28, 2012. 

Kathleen Sebelius, 

Secretary. 

For the reasons stated in the 

preamble, the Centers for Disease 

Control and Prevention, United States 

Department of Health and Human 

Services, amends 42 CFR part 73 as 

follows: 

PART 73—POSSESSION, USE, AND 

TRANSFER OF 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. Add § 73.0 to read as set forth 

below. 

§ 73.0 Applicability and related 

requirements. 

All individuals and entities that 

possess SARS-CoV, Lujo virus, or 

Chapare virus must provide notice to 

CDC regarding their possession of 

SARS-CoV, Lujo virus, or Chapare virus 

on or before November 5, 2012. 

Currently registered individuals and 

entities possessing SARS-CoV, Lujo 

virus, or Chapare virus must meet all 

the requirements of this part by 

December 4, 2012. All previously 

unregistered individuals and entities 

possessing SARS-CoV, Lujo virus, or 

Chapare virus must meet all of the 

requirements of this part by April 3, 

2013. 

■ 3. Section 73.1 is amended by adding, 

in alphabetical order, definitions of 

Conotoxins, Information security, 

Occupational exposure, Recombinant 

nucleic acids, Security barrier, and 

Synthetic nucleic acids to read as set 

forth below. 

§ 73.1 Definitions. 

* * * * * 

Conotoxins means short, paralytic 

alpha conotoxins containing the 

following amino acid sequence 

X1CCX2PACGX3X4X5X6CX7, whereas: 

(1) C = Cysteine residues are all present as 

disulfides, with the 1st and 3rd Cysteine, 

and the 2nd and 4th Cysteine forming 

specific disulfide bridges; 

(2) The consensus sequence includes known 

toxins a-MI and a-GI (shown above) as 

well as a-GIA, Ac1.1a, a-CnIA, a-CnIB; 

(3) X1 = any amino acid(s) or Des-X; 

(4) X2 = Asparagine or Histidine; 

(5) P = Proline; 

(6) A = Alanine; 

(7) G = Glycine; 

(8) X3 = Arginine or Lysine; 

(9) X4 = Asparagine, Histidine, Lysine, 

Arginine, Tyrosine, Phenylalanine or 

Tryptophan; 

(10) X5 = Tyrosine, Phenylalanine, or 

Tryptophan; 

(11) X6 = Serine, Threonine, Glutamate, 

Aspartate, Glutamine, or Asparagine; 

(12) X7 = Any amino acid(s) or Des X; and 

(13) ‘‘Des X’’ = ‘‘an amino acid does not have 

to be present at this position.’’ For 

example if a peptide sequence were 

XCCHPA then the related peptide 

CCHPA would be designated as Des-X. 

* * * * * 

Information security means 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 

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. 

Occupational exposure means any 

reasonably anticipated skin, eye, 

mucous membrane, parenteral contact, 

or respiratory aerosol exposure to select 

agents or toxins that may result from the 

performance of an employee’s duties. 

* * * * * 

Recombinant nucleic acids means: 

(1) Molecules that are constructed by 

joining nucleic acid molecules and that 

can replicate in a living cell or 

(2) Molecules that result from the 

replication of those described in 

paragraph (1) of this definition. 

* * * * * 

Security barrier means a physical 

structure that is designed to prevent 

entry by unauthorized persons. 

* * * * * 

Synthetic nucleic acids means: 

(1) Molecules that are chemically or 

by other means synthesized or 

amplified, including those that are 

chemically or otherwise modified but 

can base pair with naturally occurring 

nucleic acid molecules (i.e., synthetic 

nucleic acids) or 

(2) Molecules that result from the 

replication of those described in 

paragraph (1) of this definition. 

* * * * * 

■ 4. 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) introductory text, 

by adding the phrase ‘‘and/or 

Synthetic’’ after the word 

‘‘Recombinant’’ each time it appears. 


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■ 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 adding a new paragraph (d)(5) to 

read as set forth below. 

■ h. By revising paragraph (e) to read as 

set forth below. 

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

the words ‘‘Lassa fever virus’’ and 

‘‘South American Haemorrhagic Fever 

virus (Junin, Machupo, Sabia, Flexal, 

Guanarito)’’ and by adding, after 

‘‘Botulinum neurotoxins,’’, the term 

‘‘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: 

Abrin 

Botulinum neurotoxins* 

Botulinum neurotoxin producing 

species of Clostridium* 

Conotoxins (Short, paralytic alpha 

conotoxins containing the following 

amino acid sequence 

X1CCX2PACGX3X4X5X6CX7) 

Coxiella burnetii 

Crimean-Congo haemorrhagic fever 

virus 

Diacetoxyscirpenol 

Eastern Equine Encephalitis virus 

Ebola virus* 

Francisella tularensis* 

Lassa fever virus 

Lujo virus 

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 

SARS-associated coronavirus (SARSCoV) 

Saxitoxin 

South American Haemorrhagic Fever 

viruses: 

Chapare 

Guanarito Junin 

Machupo 

Sabia 

Staphylococcal enterotoxins (subtypes 

A–E) 

T–2 toxin 

Tetrodotoxin 

Tick-borne encephalitis virus 

Far Eastern subtype 

Siberian subtype 

Kyasanur Forest disease virus 

Omsk haemorrhagic fever virus 

Variola major virus (Smallpox virus) * 

Variola minor virus (Alastrim) * 

Yersinia pestis * 

* * * * * 

(d) * * * 

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

the aggregate amount of the toxin under 

the control of a principal investigator, 

treating physician or veterinarian, or 

commercial manufacturer or distributor 

does not, at any time, exceed the 

following amounts: 100 mg of Abrin; 0.5 

mg of Botulinum neurotoxins; 100 mg of 

Conotoxins (Short, paralytic alpha 

conotoxins containing the following 

amino acid sequence 

X1CCX2PACGX3X4X5X6CX7); 1,000 mg 

of Diacetoxyscirpenol; 100 mg of Ricin; 

100 mg of Saxitoxin; 5 mg of 

Staphylococcal enterotoxins (subtypes 

A–E); 1,000 mg of T–2 toxin; or 100 mg 

of Tetrodotoxin. 

(i) The amounts 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. 

(ii) 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 this 

part. 

(4) An animal inoculated with or 

exposed to an HHS select toxin. 

(5) Any South American genotypes of 

Eastern Equine Encephalitis Virus and 

any West African Clade of Monkeypox 

virus provided that the individual or 

entity can verify that the agent is within 

the exclusion category. 

(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. 

* * * * * 

■ 5. 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) 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 adding a new paragraph (d)(3) to 

read as set forth below. 

■ f. By revising paragraph (e) to read as 

set forth below. 

■ g. 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, after 

‘‘Bacillus anthracis’’, the terms 

‘‘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*; 

Bacillus anthracis (Pasteur strain); 

Brucella abortus; 

Brucella melitensis; 

Brucella suis; 

Burkholderia mallei*; 

Burkholderia pseudomallei*; 

Hendra virus; 

Nipah virus; 

Rift Valley fever virus; 

Venezuelan equine encephalitis virus 

* * * * * 

(d) * * * 

(3) Any subtypes of Venezuelan 

equine encephalitis virus except for 

Subtypes IAB or IC provided that the 

individual or entity can verify that the 

agent is within the exclusion category. 

(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 


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61112 Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 

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. 

* * * * * 

■ 6. Section 73.5 is amended as follows: 

■ a. By amending paragraph (a)(3)(i) to 

remove the words ‘‘Lassa fever virus’’ 

and ‘‘South American Haemorrhagic 

Fever viruses (Junin, Machupo, Sabia, 

Flexal, Guanarito)’’ and by adding, after 

‘‘Botulinum neurotoxins,’’ the term 

‘‘Botulinum neurotoxin producing 

species of Clostridium.’’ 

■ b. By revising paragraph (e) to read as 

set forth below. 

§ 73.5 Exemptions for HHS select agents 

and toxins. 

* * * * * 

(e) The HHS Secretary may 

temporarily exempt an individual or 

entity from the requirements of this part 

based on a determination that the 

exemption is necessary to provide for 

the timely participation of the 

individual or entity in response to a 

domestic or foreign public health 

emergency. With respect to the 

emergency involved, the exemption may 

not exceed 30 calendar days, except that 

one extension of an additional 30 

calendar days may be granted. 

■ 7. Section 73.6 is amended as follows: 

■ a. By amending (a)(3)(i) to remove the 

words ‘‘Brucella melitensis, Hendra 

virus, Nipah virus, Rift Valley fever 

virus, or Venezuelan equine 

encephalitis virus’’ and adding, after 

‘‘Bacillus anthracis’’, the terms 

‘‘Burkholderia mallei’’ and 

‘‘Burkholderia pseudomallei’’ in their 

place. 

■ b. By revising paragraph (e) to read as 

set forth below. 

§ 73.6 Exemptions for overlap select 

agents and toxins. 

* * * * * 

(e) The HHS Secretary may 

temporarily exempt an individual or 

entity from the requirements of this part 

based on a determination that the 

exemption is necessary to provide for 

the timely participation of the 

individual or entity in response to a 

domestic or foreign public health 

emergency. With respect to the 

emergency involved, the exemption may 

not exceed 30 calendar days, except that 

one extension of an additional 30 

calendar days may be granted. 

* * * * * 

■ 8. Section 73.9 is amended as follows: 

■ a. In paragraph (a)(4), by removing the 

word ‘‘and.’’ 

■ b. By redesignating paragraph (a)(5) as 

paragraph (a)(6). 

■ c. By adding a new paragraph (a)(5) to 

read as set forth below. 

■ d. By revising the first sentence of 

paragraph (b) to read as set forth below. 

■ e. In paragraph (c)(1), by removing the 

words ‘‘Brucella melitensis,’’ ‘‘Hendra 

virus,’’ ‘‘Lassa fever virus,’’ ‘‘Nipah 

virus,’’ ‘‘Rift Valley fever virus,’’ ‘‘South 

American Haemorrhagic Fever viruses 

(Junin, Machupo, Sabia, Flexal, 

Guanarito),’’ and ‘‘Venezuelan equine 

encephalitis virus’’ and adding, after 

‘‘Botulinum neurotoxins,’’ the terms 

‘‘Botulinum neurotoxin producing 

species of Clostridium, Burkholderia 

mallei, Burkholderia pseudomallei’’. 

§ 73.9 Responsible Official. 

(a) * * * 

(5) Have a physical (and not merely a 

telephonic or audio/visual) presence at 

the registered entity to ensure that the 

entity is in compliance with the select 

agent regulations and be able to respond 

in a timely manner to onsite incidents 

involving select agents and toxins in 

accordance with the entity’s incident 

response plan, 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. 

* * * 

* * * * * 

■ 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 (j), 

by removing the word ‘‘five’’ and adding 

in its place ‘‘three’’. 

§ 73.10 Restricting access to select agents 

and toxins; security risk assessments. 

* * * * * 

(e) A person with a valid approval 

from the HHS Secretary or 

Administrator to have access to select 

agents and toxins may request, through 

his or her Responsible Official, that the 

HHS Secretary or Administrator provide 

their approved access 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 (g) and (h), respectively 

and by revising newly redesignated 

paragraph (g) to read as set forth below. 

■ e. By adding new paragraphs (e) and 

(f) 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, 

including arthropods, 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 describe procedures for how the 

entity will notify the appropriate 

Federal, State, or local law enforcement 

agencies of such activity. 

(9) Contain provisions for information 

security that: 

(i) Ensure that all external 

connections to systems which manage 

security for the registered space are 

isolated or have controls that permit 

only authorized and authenticated 

users; 

(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 


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their access to select agents and toxins 

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 which manage access to 

registered spaces in § 73.11 or records in 

§ 73.17; 

(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, surveillance 

devices, and/or systems that manage the 

requirements of section 17 of this part 

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) Entities must conduct complete 

inventory audits of all affected select 

agents and toxins in long-term storage 

when any of the following occur: 

(1) Upon the physical relocation of a 

collection or inventory of select agents 

or toxins for those select agents or 

toxins in the collection or inventory; 

(2) Upon the departure or arrival of a 

principal investigator for those select 

agents and toxins under the control of 

that principal investigator; or 

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

select agent or toxin, all select agents 

and toxins under the control of that 

principal investigator. 

(f) 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 employees with 

access to Tier 1 select agents and toxins 

on entity policies and procedures for 

reporting, evaluation, and corrective 

actions concerning the assessment of 

personnel suitability; 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 the following 

security enhancements: 

(i) Procedures that will limit access to 

a Tier 1 select agent or toxin to only 

those individuals who are approved by 

the HHS Secretary or Administrator, 

following a security risk assessment by 

the Attorney General, have had an 

entity-conducted pre-access suitability 

assessment, and are subject to the 

entity’s procedures for ongoing 

suitability assessment; 

(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 that 

are based on the entity’s site-specific 

risk assessment; 

(iv) A minimum of three security 

barriers where each security barrier 

adds to the delay in reaching secured 

areas where select agents and toxins are 

used or stored. One of the security 

barriers must be monitored in such a 

way as to detect intentional and 

unintentional circumventing of 

established access control measures 

under all conditions (day/night, severe 

weather, etc.) The final barrier must 

limit access to the select agent or toxin 

to personnel approved by the HHS 

Secretary or Administrator, following a 

security risk assessment by the Attorney 

General. 

(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) For powered access control 

systems, describe procedures to ensure 

that security is maintained in the event 

of the failure of access control systems 

due to power disruption affecting 

registered space; 

(viii) The entity must: 

(A) Determine that the response time 

for security forces or local police will 

not exceed 15 minutes or 

(B) Provide security barriers that are 

sufficient to delay unauthorized access 

until the response force arrives in order 

to safeguard the select agents and toxins 

from theft, intentional release, or 

unauthorized access. The response time 

is measured from the time of an 

intrusion alarm, or report of a security 

incident, to the arrival of the responders 

at the first security barrier. 

(5) Entities that possess Variola major 

virus and Variola minor virus must have 

the following additional security 

requirements: 

(i) Require personnel with 

independent unescorted 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 to 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 


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2Nothing in this section is meant to supersede or 

preempt incident response requirements imposed 

by other statutes or regulations. 

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-evident 

systems; 

(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; and 

(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. 

(g) In developing a security plan, an 

individual or entity should consider the 

document entitled, ‘‘Security Guidance 

for Select Agent or Toxin Facilities.’’ 

The document is available on the 

National Select Agent Registry Web site 

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 paragraphs (c)(1), (2), 

and (3) to read as set forth below. 

■ c. By redesignating paragraph (d) as 

paragraph (e). 

■ d. 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 (including arthropods) 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 National 

Select Agent Registry Web site at 

http://www.selectagents.gov. 

(2) The Occupational Safety and 

Health Administration (OSHA) 

regulations in 29 CFR parts 1910.1200 

and 1910.1450. This document is 

available on the National Select Agent 

Registry Web site at http:// 

www.selectagents.gov. 

(3) The ‘‘NIH Guidelines for Research 

Involving Recombinant DNA 

Molecules,’’ (NIH Guidelines). This 

document is available on the National 

Select Agent Registry Web site 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. 

* * * * * 

■ 12. Section 73.13 is amended as 

follows: 

■ a. In paragraph (a), add the phrase ‘‘, 

or possess products (i.e., select agents 

that are not known to acquire the 

resistance naturally, if such acquisition 

could compromise the control of disease 

agents in humans, veterinary medicine, 

or agriculture, or recombinant and/or 

synthetic nucleic acids 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. By revising paragraph (b) to read as 

set forth below. 

§ 73.13 Restricted experiments. 

* * * * * 

(b) Restricted experiments: 

(1) Experiments that involve the 

deliberate transfer of, or selection for, a 

drug resistance trait to select agents that 

are not known to acquire the trait 

naturally, if such acquisition could 

compromise the control of disease 

agents in humans, veterinary medicine, 

or agriculture. 

(2) Experiments involving the 

deliberate formation of synthetic or 

recombinant nucleic acids containing 

genes for the biosynthesis of select 

toxins lethal for vertebrates at an LD[50] 

< 100 ng/kg body weight. 

* * * * * 

■ 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 paragraphs (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 

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, and other natural and man-made 

events. 

(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 (including 

arthropods) 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 procedures for how the entity 

will notify the appropriate Federal, 

State, or local law enforcement agencies 

of suspicious activity that may be 

criminal in nature and related to the 

entity, its personnel, or its select agents 

or toxins. 

* * * * * 

■ 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 to: 

(1) 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; and 


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Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 61115 

(2) 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 for individuals with 

access approval from the HHS Secretary 

or Administrator 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 toxins 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 paragraphs (f), (g), 

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

(g) respectively. 

■ b. In newly 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 packaging of the 

select agent(s) and toxin(s) is performed 

by an individual approved by the HHS 

Secretary or Administrator to have 

access to select agents and toxins and is 

in compliance with all applicable laws 

concerning packaging. 

* * * * * 

(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) must: 

(1) Transfer the amounts 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. 

(2) Report 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 

§ 73.3(d) of this part. 

■ 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 organisms 

containing recombinant and/or 

synthetic nucleic acids) held in longterm 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 accounting 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. 

[FR Doc. 2012–24389 Filed 10–2–12; 11:15 am] 

BILLING CODE 4163–18–P 


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