Vol. 77 Friday, 

No. 194 October 5, 2012 

Part II 

Department of Agriculture 

Animal and Plant Health Inspection Service 

7 CFR Part 331 

9 CFR Part 121 

Agricultural Bioterrorism Protection Act of 2002; Biennial Review and 

Republication of the Select Agent and Toxin List; Amendments to the 

Select Agent and Toxin Regulations; Final Rule 


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61056 Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 

1To view the ANPR and the comments we 

received, go to http://www.regulations.gov/ 

#!docketDetail;D=APHIS–2009–0070. 

2To view the proposed rule and the comments 

we received, go to http://www.regulations.gov/ 

#!docketDetail;D=APHIS–2009–0070. 

DEPARTMENT OF AGRICULTURE 

Animal and Plant Health Inspection 

Service 

7 CFR Part 331 

9 CFR Part 121 

[Docket No. APHIS–2009–0070] 

RIN 0579–AD09 

Agricultural Bioterrorism Protection 

Act of 2002; Biennial Review and 

Republication of the Select Agent and 

Toxin List; Amendments to the Select 

Agent and Toxin Regulations 

AGENCY: Animal and Plant Health 

Inspection Service, USDA. 

ACTION: Final rule. 

SUMMARY: In accordance with the 

Agricultural Bioterrorism Protection Act 

of 2002, we are amending and 

republishing the list of select agents and 

toxins that have the potential to pose a 

severe threat to animal or plant health, 

or to animal or plant products. The Act 

requires the biennial review and 

republication of the list of select agents 

and toxins and the revision of the list as 

necessary. This action implements the 

findings of the third biennial review of 

the list. In addition, we are reorganizing 

the list of select agents and toxins based 

on the relative potential of each select 

agent or toxin to be misused to 

adversely affect human, plant, or animal 

health. Such tiering of the list allows for 

the optimization of security measures 

for those select agents or 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. We are also making a 

number of amendments to the 

regulations, including the addition of 

definitions and clarification of language 

concerning security, training, biosafety, 

biocontainment, and incident response. 

These changes will increase the 

usability of the select agent regulations 

as well as provide for enhanced program 

oversight. 

DATES: The amendments to 7 CFR 331.1 

through 331.10, 331.13, and 331.16 

through 331.20 and 9 CFR 121.1 through 

121.10, 121.13, 121.16, 121.17, and 

121.20 are effective December 4, 2012. 

The remaining provisions of this final 

rule are effective April 3, 2013. 

FOR FURTHER INFORMATION CONTACT: Mr. 

Charles L. Divan, Acting Director, 

APHIS Agriculture Select Agent 

Program, APHIS, 4700 River Road Unit 

2, Riverdale, MD 20737–1231; (301) 

851–3300, option 1. 

SUPPLEMENTARY INFORMATION: 

Executive Summary 

On July 29, 2010, we published in the 

Federal Register (75 FR 44724–44725, 

Docket No. APHIS–2009–0070) an 

advance notice of proposed rulemaking 

and request for comments (ANPR)1 and 

On October 3, 2011, we published in the 

Federal Register (76 FR 61228–61244, 

Docket No. APHIS–2009–0070) a 

proposal2 regarding our intent to amend 

and republish the list of select agents 

and toxins that have the potential to 

pose a severe threat to animal or plant 

health, or to animal or plant products, 

reorganize the list of select agents and 

toxins based on the relative potential of 

each select agent or toxin to be misused 

to adversely affect human, plant, or 

animal health, and amend the 

regulations in order to add definitions 

and clarify language concerning 

security, training, biosafety, 

biocontainment, and incident response. 

Specifically, the ANPR solicited 

comments regarding whether there are 

other select agents or toxins that should 

be added to the Plant Protection and 

Quarantine (PPQ) and Veterinary 

Services (VS) lists of select agents and 

toxins, whether any of the select agents 

or toxins on the PPQ or VS lists should 

be removed, whether the PPQ and VS 

lists of select agents and toxins should 

be tiered based on the relative 

bioterrorism risk presented by each 

select agent or toxin, and whether the 

security requirements for select agents 

or toxins in the highest tier should be 

stratified based on type of use or other 

factors. Comments received as a result 

of the ANPR were used in order to 

inform our discussions on the content of 

the select agent list and our 

determination regarding reorganization 

of the list in the proposed rule. We 

solicited comments concerning our 

proposal for 60 days ending December 

2, 2011. We reopened and extended the 

deadline for comments until January 17, 

2012, in a document published in the 

Federal Register on December 15, 2011 

(76 FR 77914, Docket No. APHIS–2009– 

0070). We received 30 comments by that 

date. They were from researchers, 

scientific organizations, laboratories, 

and universities. 

Changes to the current regulations 

detailed in this final rule include: 

1. Modification of the select agent and 

toxin list: 

• The following agents would no 

longer be considered PPQ select agents 

or toxins, or would be excluded from 

compliance with the select agent 

regulations: Any subspecies of Ralstonia 

solanacearum except race 3, biovar 2 

and all subspecies of Sclerophthora 

rayssiae except var. zeae, and Xylella 

fastidiosa, citrus variegated chlorosis 

(CVC) strain. 

• The following agents would no 

longer be considered VS select agents or 

toxins, or would be excluded from 

compliance with the select agent 

regulations: Any low pathogenic strains 

of avian influenza virus, any strain of 

Newcastle disease virus which does not 

meet the criteria for virulent Newcastle 

disease virus, all subspecies 

Mycoplasma capricolum except 

subspecies capripneumoniae 

(contagious caprine pleuropneumonia), 

and all subspecies Mycoplasma 

mycoides except subspecies mycoides 

small colony (Mmm SC) (contagious 

bovine pleuropneumonia), Akabane 

virus; Bluetongue virus (exotic), Bovine 

spongiform encephalopathy agent; 

Camel pox virus; Ehrlichia ruminantium 

(Heartwater); Japanese encephalitis 

virus; Malignant catarrhal fever virus 

(Alcelaphine herpesvirus type 1); 

Menangle virus; and Vesicular 

stomatitis virus (exotic): Indiana 

subtypes VSV–IN2, VSV–IN3. 

• The following agent would no 

longer be considered a VS/Department 

of Health and Human Services (HHS) 

overlap select agent: Venezuelan Equine 

Encephalitis Virus (subtypes ID and IE). 

2. Tiering of the select agent and toxin 

lists: 

Tier 1 select agents and toxins: 

• PPQ select agents and toxins: None. 

• VS select agents and toxins: Footand-mouth disease virus and Rinderpest 

virus. 

• VS/HHS overlap select agents and 

toxins: Bacillus anthracis, Burkholderia 

mallei, and Burkholderia pseudomallei. 

3. Establishing physical security 

standards for entities possessing Tier 1 

select agents and toxins, including the 

requirement to conduct pre-access 

assessments and ongoing 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: Entities affected by 

the rule include research and diagnostic 

facilities; Federal, State, and university 

laboratories; and private commercial 

and non-profit enterprises. The 

regulations require registering the 


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Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 61057 

3To view the proposed rule and the comments 

we received, go to http://www.regulations.gov/ 

#!docketDetail;D=APHIS-2009-0070. 

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 rule 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. APHIS and HHS 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 of 

the Regulatory Impact Analysis located 

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

www.selectagents.gov. 

Benefits of the Rule: The objectives of 

the final rule is 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. 

Background 

The Public Health Security and 

Bioterrorism Preparedness and 

Response Act of 2002 (referred to below 

as the Bioterrorism Response Act) 

provides for the regulation of certain 

biological agents that have the potential 

to pose a severe threat to both human 

and animal health, to animal health, to 

plant health, or to animal and plant 

products. The Animal and Plant Health 

Inspection Service (APHIS) has the 

primary responsibility for implementing 

the provisions of the Act within the 

Department of Agriculture (USDA). 

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. Plant Protection and 

Quarantine (PPQ) select agents and 

toxins are those that have the potential 

to pose a severe threat to plant health 

or plant products. Overlap select agents 

and toxins are those that have been 

determined to pose a severe threat to 

human and animal health or animal 

products. Overlap select agents are 

subject to regulation by both APHIS and 

the Centers for Disease Control and 

Prevention (CDC), which has the 

primary responsibility for implementing 

the provisions of the Act for the 

Department of Health and Human 

Services (HHS). 

Subtitle B (which is cited as the 

‘‘Agricultural Bioterrorism Protection 

Act of 2002’’ and referred to below as 

the Act), section 212(a), provides, in 

part, that the Secretary of Agriculture 

(the Secretary) must establish by 

regulation a list of each biological agent 

and each toxin that the Secretary 

determines has the potential to pose a 

severe threat to animal or plant health, 

or to animal or plant products. 

Paragraph (a)(2) of section 212 requires 

the Secretary to review and republish 

the list every 2 years and to revise the 

list as necessary. In this document, we 

are amending and republishing the list 

of select agents and toxins based on the 

findings of our third biennial review of 

the list. 

In determining whether to include an 

agent or toxin on the list, the Act 

requires that the following criteria be 

considered: 

• The effect of exposure to the agent 

or the toxin on animal and plant health, 

and on the production and marketability 

of animal or plant products; 

• The pathogenicity of the agent or 

the toxin and the methods by which the 

agent or toxin is transferred to animals 

or plants; 

• The availability and effectiveness of 

pharmacotherapies and prophylaxis to 

treat and prevent any illness or disease 

caused by the agent or toxin; and 

• Any other criteria that the Secretary 

considers appropriate to protect animal 

or plant health, or animal or plant 

products. 

We use the term ‘‘select agents and 

toxins’’ throughout the preamble of this 

final rule. Unless otherwise specified, 

the term ‘‘select agents and toxins’’ will 

refer to all agents or toxins listed by 

APHIS. When it is necessary to specify 

the type of select agent or toxin, we will 

use the following terms: ‘‘PPQ select 

agents and toxins’’ (for the plant agents 

and toxins listed in 7 CFR 331.3), ‘‘VS 

select agents and toxins’’ (for the animal 

agents and toxins listed in 9 CFR 121.3), 

or ‘‘overlap select agents and toxins’’ 

(for the agents and toxins listed in both 

9 CFR 121.4 and 42 CFR 73.4). 

On October 3, 2011, we published in 

the Federal Register (76 FR 61228– 

61244, Docket No. APHIS–2009–0070) a 

proposal 3 to amend and republish the 

list of select agents and toxins that have 

the potential to pose a severe threat to 

animal or plant health, or to animal or 

plant products, reorganize the list of 

select agents and toxins based on the 

relative potential of each select agent or 

toxin to be misused to adversely affect 

human, plant, or animal health, and 

amend the regulations in order to add 

definitions and clarify language 

concerning security, training, biosafety, 

biocontainment, and incident response. 

We solicited comments concerning 

our proposal for 60 days ending 

December 2, 2011. We reopened and 

extended the deadline for comments 

until January 17, 2012, in a document 

published in the Federal Register on 

December 15, 2011 (76 FR 77914, 

Docket No. APHIS–2009–0070). We 

received 30 comments by that date. 

They were from researchers, scientific 

organizations, laboratories, and 

universities. They are discussed below 

by topic. 

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 useful in developing 

such guidance documents. We received 

a number of comments on the issue of 

guidance, which are discussed below. 

Two commenters suggested the use of 

specific documents in creating 

guidance: The Laboratory Biorisk 

Management Standard, which was 


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61058 Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations 

4To view the ANPR and the comments we 

received, go to http://www.regulations.gov/ 

#!docketDetail;D=APHIS-2009-0070. 

developed by the European Committee 

for Standardization, and the report 

‘‘Guidance for Enhancing Personnel 

Reliability and Strengthening the 

Culture of Responsibility,’’ which was 

developed by the National Science 

Advisory Board for Biosecurity. 

We agree with the commenters and 

have utilized both sources in developing 

guidance. 

One commenter stated that the select 

agent program should develop a 

standardized template that addresses 

each item required by the regulations, 

both for regulated entities and 

inspectors. The commenter went on to 

say that the templates should be posted 

on the select agent Web site. 

The National Select Agent Registry at 

www.selectagents.gov includes 

checklists, guidance documents, and 

templates that we have developed to aid 

entities in meeting the requirements of 

the regulations. The select agent 

program also conducts regular inspector 

training in order to standardize 

inspector understanding of the 

regulations and inspection process. We 

accept entity feedback regarding the 

inspection process and incorporate it 

into our training program as 

appropriate. 

Another commenter stated that the 

involvement of regulated entities in the 

development of guidance is crucial, as 

it will ensure that the new regulations 

may be implemented without 

unsustainable increases in cost to those 

entities. 

The guidance documents developed 

in conjunction with this rule are, in 

part, a response to the questions and 

issues raised by the commenters 

regarding various aspects of the 

proposed rule. We also consulted HHS 

and USDA subject matter experts and 

other sources including National 

Science Advisory Board for Biosecurity, 

the National Academies, the Department 

of Defense Security Engineering 

Facilities Planning Manual, and Director 

of Central Intelligence Directive Number 

6/9. Regarding the commenter’s cost 

concerns, the guidance developed by 

the select agent program does not set out 

a prescriptive series of procedures that 

must be followed by all regulated 

entities; rather, it establishes examples 

of ways in which an entity may choose 

to meet the requirements of the 

regulations. We have purposefully left 

the regulations in their general state in 

order to allow for the wide variety of 

regulated entities to meet the regulatory 

standard in a way that is most costeffective for each. 

PPQ Select Agents and Toxins 

We proposed to amend the list of PPQ 

select agents and toxins listed in 7 CFR 

331.3 by removing Xylella fastidiosa, 

citrus variegated chlorosis (CVC) strain, 

from the list as it no longer meets the 

criteria for use as an agroterrorism 

agent. 

One commenter stated that the 

scientific basis for the removal of 

Xylella fastidiosa from the list was 

unclear and requested clarification 

concerning our decision. The 

commenter additionally stated that if 

the review process for such removal 

were to be transparent, with expert 

opinion from the public and private 

sector, including a sound scientific 

analysis and an assessment of the 

biosecurity risk of each agent, other 

plant pathogens on the list of select 

agents and toxins could potentially be 

removed. 

We are making no changes as a result 

of this comment. Each agent on the 

select agent and toxin list was 

considered for retention or removal 

based on a variety of factors, including, 

but not limited to, the scientific 

concerns cited by the commenter. 

Further, the select agent program did 

employ subject-matter experts as part of 

the decision-making process as 

recommended by the commenter in 

addition to soliciting public comment. 

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 evaluation 

included assessments of morbidity and 

mortality, communicability, low 

infectious dose, availability of 

countermeasures, and economic impact 

of a potential attack. Each agent and 

toxin was then assessed for its ‘‘risk of 

deliberate misuse,’’ including its history 

of weaponization and/or known interest 

by State or non-State adversaries. These 

evaluations, combined with input 

received as a result of the publication of 

an advance notice of proposed 

rulemaking and request for comments 

(ANPR) 4 in the Federal Register on July 

29, 2010, and relevant findings in recent 

government and non-government 

reports, formed the basis for 

deliberations concerning which agents 

should constitute the list. It is important 

to note that removal of pathogens from 

the list of select agents and toxins does 

not mean that they are not of potential 

concern, but rather that the risk they 

represent has been reevaluated using the 

above criteria. Reduction of the list is 

meant to decrease the burden on 

researchers and focus attention on 

agents and toxins judged to be of 

greatest biosecurity concern. 

The list of PPQ select agents and 

toxins includes an entry for 

Xanthomonas oryzae. While we did not 

propose any changes to the entry for 

Xanthomonas oryzae, one commenter 

stated that it should be removed from 

the list of select agents and toxins and 

offered a number of arguments, which 

are discussed below. 

The commenter proposed the removal 

of Xanthomonas oryzae based on the 

assertion that Xanthomonas oryzae 

populations are adapted only to local 

conditions and do not persist upon 

introduction to new environments. 

Given that the major natural host for 

Xanthomonas oryzae is rice, the 

commenter also compared cultivation 

practices utilized in domestic 

commercial rice production with those 

utilized in Asian commercial rice 

production. The commenter argued that 

domestic commercial cultivation 

practices eliminate transmission of the 

pathogen since rice seeds are directly 

planted whereas in Asia rice seedlings 

are cultivated elsewhere and then 

transplanted, and wounds created 

during such handling and transplant are 

important modes of transmission for the 

pathogen to healthy seedlings. In 

addition, the commenter said that 

domestic weather patterns are not 

conducive to dissemination and that 

quarantines can prevent seed-borne 

disease. The commenter claimed that 

field-to-field spread of Xanthomonas 

oryzae in Asia is largely dependent on 

the strong winds and driving rains that 

occur frequently during typhoon season. 

We are making no changes to the 

regulations as a result of this comment. 

Natural spread or persistence of the 

pathogen in a particular location is not 

at issue; it is the risk of deliberate 

misuse leading to the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence. The issue of standard 

commercial planting practices for rice in 

a domestic versus Asian setting is not 

relevant to the discussion of 

Xanthomonas oryzae’s potential for use 

as a biological weapon. APHIS analyzed 

and assessed this pathogen using the 

criteria discussed earlier in this 

document. Based on that analysis and 

assessment and the knowledge that 

Xanthomonas oryzae has been modified 

for use as a biological weapon in the 

past, it has been retained on the list of 

PPQ select agents and toxins. 

The commenter also stated that 

Xanthomonas oryzae should be 


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removed from the list of select agents 

and toxins because it is endemic in the 

United States and any foreign strains 

introduced in the future would prove 

unlikely to establish and spread. 

While we disagree with the 

commenter’s assertion regarding 

Xanthomonas oryzae’s pathogenicity, 

these arguments are unrelated to the 

work of the select agent program as a 

whole as the select agent regulations do 

not allow for the environmental release 

of listed agents and toxins. Whether or 

not a given select agent or toxin is 

endemic in the United States is not the 

only determining factor in the select 

agent or toxin’s inclusion on the list. 

The regulations govern use of listed 

select agents and toxins in laboratory 

settings only. In this regard, the case for 

maintaining Xanthomonas oryzae on 

the list of those select agents and toxins 

whose deliberate misuse represents the 

most significant potential for mass 

casualties or devastating effects to the 

economy, critical infrastructure, or 

public confidence, is compelling as 

work was done on Xanthomonas oryzae 

in the 1970s which led to its 

classification as a bioterrorism agent by 

the security community. 

The list of PPQ select agents and 

toxins includes an entry for Ralstonia 

solanacearum, race 3, biovar 2. While 

we did not propose any changes to the 

entry for Ralstonia solanacearum, race 

3, biovar 2, five commenters stated that 

it should be removed from the list of 

select agents and toxins. 

The commenters argued that, based 

on the biological and historical climate 

data for North America, Ralstonia 

solanacearum, race 3, biovar 2 does not 

have the potential to pose a severe 

threat to plant health or plant products 

in the context of U.S. agriculture. The 

commenters stated that Ralstonia 

solanacearum, race 3, biovar 2 is only 

a serious problem in the developing 

world in those areas of cool highland 

tropics where annual temperature 

profiles differ significantly from those 

found in the major potato growing 

regions in the United States (i.e., 

Colorado, Idaho, Maine, Minnesota, 

North Dakota, and Wisconsin). The 

commenters argued that, unlike the 

northern States, the cool highland 

tropics experience few hard freezes and 

no long winters. Since, the commenters 

claimed, epidemiological and laboratory 

research data show that Ralstonia 

solanacearum, race 3, biovar 2 is 

intolerant of freezing and freeze-thaw 

cycles and does not generally survive 

winters in regions with sustained low 

temperatures, the bacterium is unlikely 

to become established in the northern 

U.S. where potatoes are commercially 

grown. 

We disagree with the commenters’ 

claim that Ralstonia solanacearum, race 

3, biovar 2 is only a serious pathogen in 

the developing world as the bacterium 

has been shown to establish itself in 

northern Europe by over-wintering in 

weeds, thereby posing a severe threat to 

Solanaceae species (e.g., potato, 

eggplant, and tomato) in cool climates 

such as those found both in northern 

Europe and North America. In addition, 

as discussed earlier in this document, 

the evaluation process for select agents 

includes broad criteria that not only 

focus on the biological characteristics of 

a given pathogen, but also that 

pathogen’s ability to produce a 

devastating effect on the economy and 

the threat that pathogen represents if it 

were to be used as a biological weapon. 

We are making no changes as a result of 

these comments. 

The commenters also stated that 

retaining Ralstonia solanacearum, race 

3, biovar 2 on the list of select agents 

and toxins would further constrain 

research in the field of Ralstonia 

research. The commenters attributed 

such listing with registration time for 

use, transfer, or possession of select 

agents and toxins in excess of 18 

months prior to the initiation of 

research and difficulty in meeting the 

registration requirements. 

We are making no changes in 

response to these comments. While 

there are added requirements 

concerning physical security, personnel 

authorization, recordkeeping, 

biocontainment, and site inspections, 

we do not believe these requirements 

will impede research as, in many cases 

these regulations serve to codify systems 

and procedures already in use by a 

majority of regulated entities. Further, 

entity registration for use, transfer, or 

possession of select agents and toxins 

does not take, nor has ever taken, 18 

months. On average, new entity 

registration takes 6 months from the 

date the request is received by the select 

agent program and the issuance of the 

registration certificate. The security risk 

assessment (SRA) takes less than 45 

days and runs parallel to the entity 

registration process. These timeframes 

are all based on the assumption that the 

entity registration submission and the 

SRA submission are complete and 

accurate for select agent program review 

prior to the required on-site inspection. 

Commenters additionally stated that 

Ralstonia solanacearum, race 3, biovar 

2 should be removed from the list for 

the same reasons that were cited for the 

proposed removal of Xylella fastidiosa, 

CVC strain. 

We are making no changes as a result 

of these comments. The decision to 

remove the CVC strain from the list of 

select agents and toxins was based on 

the completion of extensive review and 

analysis of the criteria for inclusion on 

the list. In particular, the creation of 

detection methods and the use of 

geostatistical analysis with relation to 

monitoring in order to facilitate a 

response to any purposeful introduction 

are both key components in our 

decision to delist CVC. As discussed 

earlier in this document, the evaluation 

process for select agents includes a 

broad number of criteria that not only 

focus on the biological characteristics of 

a given pathogen but also that 

pathogen’s ability to produce a 

devastating effect on the economy and 

the threat that pathogen represents if it 

were to be used as a biological weapon. 

Based on that analysis and assessment 

Ralstonia solanacearum, race 3, biovar 

2 will remain on the list of select agents 

and toxins. 

Commenters said that eradicating 

Ralstonia solanacearum, race 3, biovar 

2 introduced into the United States 

through infected geraniums cost 

commercial greenhouses and importers 

millions of dollars as a direct result of 

its presence on the list of select agents 

and toxins. 

We are making no changes as a result 

of these comments. The presence of 

Ralstonia solanacearum, race 3, biovar 

2 on the list of select agents and toxins 

had no bearing on the eradication 

program instituted by APHIS. The cost 

of this eradication program to 

commercial greenhouses and importers 

was the same as the cost of eradicating 

any other quarantine plant pathogen not 

known to be present in the United 

States. 

Identification of Strains 

The list of VS select agents and toxins 

includes an entry for virulent Newcastle 

disease virus. While we did not propose 

any changes to the entry for virulent 

Newcastle disease virus, one commenter 

stated that, by not considering all forms 

of Newcastle disease virus as select 

agents, APHIS has created a period of 

uncertainty prior to the completion of 

the sequencing necessary to identify 

whether a form of Newcastle disease 

virus is virulent or not. The commenter 

requested clarification as to whether 

laboratories would be required to treat 

uncharacterized Newcastle disease virus 

as a select agent given this uncertainty. 

We agree with the commenter’s point. 

We have therefore revised the list of VS 

only select agents and toxins in order to 

list certain select agents and toxins not 

by specific strains but by the generic 


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taxonomic classifications for those 

select agents. The specific VS only 

select agents and toxins affected are: 

Avian influenza virus (highly 

pathogenic), mycoplasma capricolum 

subspecies capripneumoniae 

(contagious caprine pleuropneumonia), 

mycoplasma mycoides subspecies 

mycoides small colony (Mmm SC) 

(contagious bovine pleuropneumonia), 

and virulent Newcastle disease virus, 

which we have altered to read avian 

influenza virus, mycoplasma 

capricolum, mycoplasma mycoides, and 

Newcastle disease virus, respectively. In 

order to capture the applicable strains, 

subtypes, or pathogenicity levels we 

have also added exemptions for those 

strains, subtypes, or pathogenicity levels 

of certain select agents and toxins which 

are not considered to have the potential 

to pose a severe threat to animal health 

or animal products. 

The list of overlap select agents and 

toxins contains an entry for Venezuelan 

equine encephalitis. One commenter 

stated that, by not considering all 

subtypes of Venezuelan equine 

encephalitis as select agents, APHIS has 

created a period of uncertainty prior to 

the completion of the typing necessary 

to identify whether a form of 

Venezuelan equine encephalitis is 

among the subtypes classified by APHIS 

as select agents. The commenter 

requested clarification as to whether 

laboratories would be required to treat 

untyped Venezuelan equine 

encephalitis as a select agent given this 

uncertainty. 

We agree with the commenter’s point. 

As stated previously, we have therefore 

revised the list of overlap select agents 

and toxins in order to list certain select 

agents and toxins not by specific strains 

but by the generic taxonomic 

classifications for those select agents. 

The specific overlap select agent is 

Venezuelan equine encephalitis virus: 

Epizootic Subtypes IAB, IC, which we 

have altered to read Venezuelan equine 

encephalitis virus. In order to capture 

the applicable strains, subtypes, or 

pathogenicity levels we have also added 

exemptions for those strains, subtypes, 

or pathogenicity levels of certain select 

agents and toxins which are not 

considered to have the potential to pose 

a severe threat to animal or human 

health or animal products. We do note 

that we have specifically included 

Bacillus anthracis (Pasteur strain) in the 

list of overlap select agents and toxins. 

This is necessary in order to distinguish 

this strain, which we do not consider to 

be a Tier 1 select agent, from all other 

strains of Bacillus anthracis, which are 

classified as Tier 1 select agents. 

Although we did not receive any 

comments on this issue as it concerns 

PPQ only select agents and toxins, in 

order to strengthen the regulations as 

discussed previously as well as to 

maintain parity between the VS and 

PPQ regulations, we are revising the list 

of PPQ only select agents and toxins in 

order to list certain select agents and 

toxins not by specific strains but by the 

generic taxonomic classifications for 

those select agents. The specific PPQ 

only select agents and toxins affected 

are: Ralstonia solanacearum, race 3, 

biovar 2 and Sclerophthora rayssiae var. 

zeae which we have altered to read 

Ralstonia solanacearum and 

Sclerophthora rayssiae, respectively. In 

order to capture the applicable strains, 

subtypes, or pathogenicity levels we 

have also added exemptions for those 

strains, subtypes, or pathogenicity levels 

of certain select agents and toxins which 

are not considered to have the potential 

to pose a severe threat to plant health 

or plant products. 

With the changes described above, we 

clearly establish that when an agent or 

toxin is initially identified to a 

taxonomic level, in the case of an agent, 

or by its toxicological properties, in the 

case of a toxin, it is regulated under the 

select agent regulations until further 

testing is accomplished to exclude the 

particular agent by strain, subtype, 

pathogenicity levels, or a particular 

toxin by properties. We believe it is 

important that laboratories treat these 

agents as select agents until further 

testing can be conducted to verify 

whether the agent is of a strain, subtype, 

or pathogenicity level that presents a 

higher level of danger to animal health 

and safety. These changes will not have 

any impact on the exemption for 

diagnostic laboratories or alter the 

process of receiving diagnostic samples 

and forwarding any potentially 

identified select agents for further 

testing. They also do not change the 

reporting criteria for those agents 

confirmed to be select agents. Finally, 

they do not change the current lists of 

select agents and toxins but alters the 

fashion in which select agents and 

toxins are listed with specific 

exemptions included to ensure that 

appropriate verification of the agents by 

strains, subtypes, or pathogenicity level 

occurs. 

VS Select Agents and Toxins 

We proposed to remove nine VS 

select agents and toxins from the list set 

out in § 121.3(b). Specifically, we 

proposed to remove the following: 

Akabane virus; Bluetongue virus 

(exotic), Bovine spongiform 

encephalopathy agent; Camel pox virus; 

Ehrlichia ruminantium (Heartwater); 

Japanese encephalitis virus; Malignant 

catarrhal fever virus (Alcelaphine 

herpesvirus type 1); Menangle virus; 

and Vesicular stomatitis virus (exotic): 

Indiana subtypes VSV–IN2, VSV–IN3. 

One commenter recommended that 

we exclude the Texas GB strain of 

Newcastle disease virus from select 

agent status. The commenter stated that 

the exclusion is warranted since, 

although Newcastle disease virus is 

widespread in the environment, there is 

little illness if a flock is exposed 

because nearly all commercial poultry is 

vaccinated against the disease. The 

commenter observed that the Texas GB 

strain of Newcastle disease virus is used 

by vaccine manufacturers as the 

challenge organism to verify the potency 

of Newcastle disease virus vaccines and 

this fact gives poultry producers a high 

degree of assurance that their flocks are 

protected against the Texas GB strain. 

Given these factors, the commenter 

concluded that the Texas GB strain is 

not a biosecurity threat to the domestic 

poultry industry, and the strain should 

be excluded from APHIS’s definition of 

virulent Newcastle disease virus. 

We are making no change in this final 

rule as a result of this comment. Texas 

GB strain of Newcastle disease virus is 

a highly virulent form of Newcastle 

disease virus and, as such, is 

appropriately included in the general 

category of ‘‘virulent Newcastle disease 

virus.’’ While vaccine manufacturers do 

use the Texas GB strain of Newcastle 

disease virus as a challenge organism for 

Newcastle disease virus vaccines, this is 

on account of its high level of virulence. 

A vaccine effective against the Texas GB 

strain of Newcastle disease virus can 

therefore be assumed to be effective 

against less virulent forms of Newcastle 

disease virus. 

The list of VS select agents and toxins 

includes an entry for avian influenza 

virus (highly pathogenic) (HPAI). While 

we did not propose any changes to the 

entry for HPAI, one commenter 

proposed that we change the guidance 

by which influenza strains are 

categorized as HPAI. The commenter 

argued that extensive evidence has been 

obtained to support the conclusion that, 

while the HA polybasic cleavage site is 

the primary determinant for HPAI 

strains, strains with removed HA 

polybasic cleavage sites have been 

created, tested, and ultimately excluded 

from select agent status. The commenter 

stated that, as a result of these 

experiments and history, APHIS should 

specify that avian influenza strains 

without the HA polybasic cleavage site 

are not HPAI viruses and, therefore, not 

subject to the select agent regulations. 


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The commenter further argued that 

continuing to consider strains of avian 

influenza with removed HA polybasic 

cleavage sites as select agents until such 

time as an exclusion is granted would 

impede vaccine availability in the event 

of an HPAI pandemic in either the 

human or avian population. The 

commenter stated that the lead 

candidates for the seed viruses that 

would be used to make vaccines against 

HPAI viruses during such an event will 

likely be attenuated strains with 

mutated polybasic cleavage sites. The 

commenter stated that the current 

process by which avian influenza 

strains that lack the polybasic cleavage 

site are granted exclusions takes weeks 

or months, an untenable timeline in the 

event of an HPAI pandemic. 

We are making no changes in 

response to this comment. APHIS 

standards are based on existing 

internationally recognized requirements 

established by the World Animal Health 

Organization (OIE). In the event of a 

future HPAI pandemic such as the one 

described by the commenter, APHIS 

would work in conjunction with HHS to 

address any vaccine availability issues. 

Finally, attenuated strains of select 

agents officially approved for human 

vaccination purposes by the Food and 

Drug Administration (FDA) or other 

recognized national or international 

organizations continue to be exempt 

from the select agent regulations as 

specified by the regulations in § 121.5(c) 

and (d). 

Overlap Select Agents and Toxins 

We proposed to modify the list of 

overlap select agents and toxins by 

removing certain subtypes of 

Venezuelan equine encephalitis virus 

from the list of overlap select agents and 

toxins set out in 9 CFR 121.4(b), and to 

clarify that only Venezuelan equine 

encephalitis subtypes IAB and IC would 

remain on the list. These subtypes 

contain the only recognized strains of 

Venezuelan equine encephalitis that can 

suddenly affect a large number of 

animals over a large area (i.e., 

epizootic). The remaining subtypes, ID 

and IE, are strains prevalent among 

existing animal populations (i.e., 

enzootic) and do not represent the same 

type of risk. Other viruses within the 

Venezuelan equine encephalitis 

complex (subtypes IF and II through IV) 

are separate viruses and are not 

included in the list of overlap select 

agents and toxins. 

Another commenter recommended 

that we remove Venezuelan equine 

encephalitis strain 3014 from the list of 

select agents and toxins. The commenter 

argued that, although strain 3014 was 

derived from a 1AB isolate, this 

molecularly cloned strain has properties 

that render it incapable of causing 

epizootic or epidemic transmission. The 

commenter stated that mutations 

selected after only a handful of passages 

make the virus avirulent in adult mice 

and dramatically increases its clearance 

from the bloodstream of mice following 

intravenous inoculation. Further, the 

vanishingly low titers of strain 3014 

consist of envelope glycoprotein gene 

mutations, which allow the strain to 

bind heparin sulfate; such binding is 

also associated with the attenuated 

phenotype of Venezuelan equine 

encephalitis strain TC–83, which is also 

derived from the 1AB Trinidad donkey 

strain by passage in culture that has 

already been excluded from select agent 

status. 

We are making no changes as a result 

of this comment. Since Venezuelan 

equine encephalitis strain 3014 is 

derived from a listed overlap select 

agent, the commenter’s proposal for its 

removal is more appropriately 

addressed via the exclusion process for 

overlap select agents and toxins as 

detailed in 9 CFR 121.6. We have 

contacted the commenter and provided 

guidance regarding how they may 

initiate this process. 

We proposed to designate Bacillus 

anthracis as a Tier 1 select agent. A 

number of commenters objected to such 

a blanket designation, arguing instead 

that the Bacillus anthracis Pasteur strain 

should be exempted from consideration 

both as a Tier 1 select agent and as a 

select agent in general. 

One commenter argued that given the 

fact that Laboratory Response Network 

(LRN) laboratories maintain live 

cultures of non-pathogenic Bacillus 

anthracis Pasteur strain for use in 

quality control testing, designation of 

Bacillus anthracis as a Tier 1 select 

agent therefore has the potential to 

impact the willingness or ability of LRN 

laboratories to maintain inventories of 

Bacillus anthracis Pasteur strain due to 

the regulatory and financial burdens 

associated with possession of Tier 1 

select agents and toxins. The commenter 

went on to state that this situation could 

potentially impact national health and 

safety given that the potential use of 

Bacillus anthracis spores as a 

bioweapon remains a viable threat and 

increased burdens, particularly on small 

laboratories, could lead to the overall 

decrease in the number of laboratories 

that would otherwise serve to ensure 

that the LRN has sufficient capacity to 

detect and respond to a deliberate 

release of Bacillus anthracis. 

Three commenters stated that the 

Bacillus anthracis Pasteur strain is 

analogous to the Bacillus anthracis 

Sterne strain, which is excluded since it 

was determined not to pose a severe 

threat to public health and safety, 

animal health, or animal products. The 

commenter argued that Bacillus 

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 via 

combination of the Pasteur strain with 

a non-regulated strain. The commenter 

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 Bacillus 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 

combination of 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 agree with the commenters that 

Bacillus anthracis Pasteur strain is 

attenuated and poses a significantly 

lower risk than wild type Bacillus 

anthracis strains. We also agree that the 

Pasteur strain is not likely to have the 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence and therefore does not meet 

the criteria used to apply the Tier 1 

designation. In addition, we note that 

the Pasteur strain has been used 

successfully as a veterinary and human 

vaccine, which further demonstrates the 

attenuation of this strain. Therefore we 

have determined that the Bacillus 

anthracis Pasteur strain should not be 

designated as a Tier 1 select agent. 

While we agree that the Bacillus 

anthracis Pasteur strain does not meet 

the criteria for inclusion as a Tier 1 

select agent, we do not agree with the 

argument that regulating the Bacillus 

anthracis Pasteur strain would not serve 

to prevent the accidental (or intentional) 

generation of a wild type Bacillus 

anthracis strain by the combination of 

the Bacillus anthracis Pasteur strain 

with the Bacillus anthracis pXO1+/ 

pXO2- Sterne strain. Retaining the 


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Bacillus anthracis 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 Bacillus anthracis 

Sterne strain could occur to produce the 

wild type phenotype of Bacillus 

anthracis de novo. Failure to retain the 

Bacillus anthracis Pasteur strain as a 

select agent could result in an 

environment in which the probability of 

creation of virulent wild type Bacillus 

anthracis strains by the combination of 

non-regulated strains would be 

enhanced. Therefore, we have chosen 

not to exclude the Bacillus anthracis 

Pasteur strain from the list of select 

agents in this rulemaking. We will 

continue to evaluate exclusion requests 

as additional information becomes 

available in this area. 

As explained above under the heading 

‘‘VS Select Agents and Toxins,’’ avian 

influenza virus (highly pathogenic) is 

currently on the list of VS only select 

agents and toxins. One commenter 

recommended that, in light of recent 

studies whereby researchers have 

generated derivatives of influenza virus 

A (H5N1) capable of efficient aerosol 

transmission, we add ‘‘Replication 

competent forms of influenza virus A 

(H5N1) capable of efficient aerosol 

transmission in ferrets or primates 

containing any portion of the coding 

regions of all eight gene segments 

[influenza virus A (H5N1) capable of 

efficient aerosol transmission in ferrets 

or primates]’’ to the list of overlap select 

agents and toxins. The commenter also 

recommended that this type of avian 

influenza virus be classified as a Tier 1 

agent given the historical 50 percent 

case-fatality rate of avian influenza virus 

A (H5N1) in humans. 

The select agent program is currently 

in discussions regarding this issue and 

may address it in future rulemaking. 

Given the stage these discussions are in, 

however, we are not making any 

changes in this final rule based on this 

comment. 

Reorganization of the Current List of 

Select Agents and Toxins 

We proposed to establish a number of 

select agents and toxins as ‘‘Tier 1’’ 

select agents and toxins within the lists 

of VS and overlap select agents and 

toxins. Specifically, we proposed to list 

foot-and-mouth disease (FMD) virus and 

rinderpest virus as Tier 1 VS select 

agents and toxins and Bacillus 

anthracis, Burkholderia mallei, and 

Burkholderia pseudomallei as Tier 1 

overlap select agents and toxins. We did 

not include PPQ select agents and 

toxins in this proposed reorganization 

because none of the PPQ select agents 

and toxins met the minimum criteria for 

inclusion on the proposed Tier 1 select 

agents and toxins list. All other select 

agents and toxins would continue to be 

subject to the current requirements 

concerning select agents and toxins. 

One commenter argued that 

Burkholderia mallei and Burkholderia 

pseudomallei should not be classified as 

Tier 1 select agents. The commenter 

stated that these two select agents do 

not represent the same level of concern 

as the other select agents proposed for 

inclusion in Tier 1 and should therefore 

be assigned non-Tier 1 status. 

Another commenter observed that 

Bacillus anthracis is less virulent than 

either Yersinia pestis or Francisella 

tularensis, which are on the list of HHS 

only select agents and toxins. The 

commenter additionally stated that the 

virulence of all three is far less than that 

of the hemorrhagic fever viruses and the 

encephalitis viruses that were not 

proposed for inclusion on the list of Tier 

1 select agents and toxins. The 

commenter stated that significant 

advances have been made in the 

development of products for 

environmental decontamination and 

prophylaxis against inhalation of 

Bacillus anthracis. 

We are making no changes to the 

regulations as a result of these 

comments. The process by which we 

determined which select agents and 

toxins should be designated as Tier 1 

was multi-faceted and we are confident 

in the results of that process. Our 

determinations were not based on one 

aspect of each of the proposed select 

agents or toxins only. In order to 

determine which select agents and 

toxins should be given Tier 1 status, a 

two-part risk analysis was conducted on 

each. 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 process included 

assessments of morbidity and mortality, 

communicability, low infectious dose, 

availability of countermeasures, and 

economic impact of a potential attack. 

Second, each select agent and toxin was 

assessed for its risk of deliberate misuse, 

including its history of weaponization 

and/or known interest by State or nonState adversaries. These evaluations, 

combined with input from public 

comments received on our July 2010 

ANPR and relevant findings in recent 

government and non-government 

reports, formed the basis for 

deliberations on which agents should 

constitute the Tier list. Agents that 

scored highly on both the public health 

and biothreat sets of criteria were 

judged to be those that were 

appropriately given a Tier 1 designation. 

Two commenters pointed out that the 

categorization of select agents and 

toxins has already been carefully 

stratified into four biological safety 

levels (BSL) as specified by the CDC, 

with each BSL based on infectivity, 

virulence, and ease of transmission of 

the material in question. The 

commenters further observed that the 

Tier 1 designation implies the existence 

of a Tier 2 category which would 

require less attention to security. The 

commenters concluded that the process 

of tiering will only add confusion and 

administrative and financial burden to 

the current BSL grouping of select 

agents and toxins. 

Two additional commenters stated 

that the proposed rule did not do 

enough to reduce the regulatory burden 

associated with non-Tier 1 agents. The 

commenters said that reduced levels of 

security requirements for personnel and 

facilities should be considered for nonTier 1 agents. 

In designating certain select agents 

and toxins as ‘‘Tier 1,’’ the select agent 

program considered and rejected the 

idea of designating the remaining select 

agents and toxins as ‘‘Tier 2.’’ The aim 

of establishing the Tier 1 category is to 

account for and respond to the 

particular risks associated with the 

agents and toxins in this category by 

increasing their handling and security 

requirements accordingly. The 

establishment of the Tier 1 category is 

in no way intended to imply that the 

non-Tier 1 select agents and toxins pose 

a lesser risk to public health and safety 

than they have previously. In 

accordance with that fact, we have not 

decreased the handling and security 

requirements for those non-Tier 1 

agents. Biosafety levels describe the 

required combination of lab practices 

and techniques, safety equipment, and 

lab facilities appropriate for the 

operations being performed using 

potentially harmful materials such as 

select agents and toxins while the Tier 

1 designation institutes security 

measures applicable to the agents and 

toxins themselves. For this reason there 

is no conflict that exists between BSL 

classifications and Tier 1 select agents 

and toxins. 

Two commenters expressed concern 

regarding the proposal to list rinderpest 

virus as a Tier 1 agent, given that there 

are already special conditions in place 

as contained in §§ 121.3(f)(3)(i), 

121.5(a)(3)(i), and 121.9(c)(1) 

concerning its handling and tracking. 

The commenters suggested that an 

alternative approach would be for 

APHIS to designate rinderpest virus as 


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a pathogen with very special handling 

requirements that is not considered to 

be part of either category of select 

agents. The commenters argued that this 

approach is justified due to the fact that 

rinderpest has now been officially 

eradicated worldwide. 

We disagree with the commenters’ 

suggestion to classify rinderpest virus as 

a separate type of agent apart from 

either of the select agent categories of 

designation. While it is true that 

rinderpest was declared to be officially 

eradicated by the OIE on May 25, 2011, 

this development does not render the 

disease any less of a concern as a select 

agent with potential for misuse. 

Enacting the suggestion that rinderpest 

virus be treated as a pathogen with 

‘‘very special handling requirements’’ 

and not as either a Tier 1 or non-Tier 1 

select agent would only serve to create 

a further level of required 

administrative oversight for regulated 

entities. 

One commenter stated that the 

proposed tiering system poses 

significant questions as to the nature of 

the risk assessment process. 

Specifically, the commenter 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. The commenter further stated 

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 are making no changes as a result 

of this comment. The relative ease by 

which exposure to a select agent or 

toxin may be treated is only one aspect 

considered by the select agent program 

when determining the tier status of 

each. The 20 criteria referenced by the 

commenter are those employed by the 

Federal Experts Security Advisory Panel 

(FESAP) in providing recommendations 

to the select agent program. The criteria 

that the FESAP used in its risk 

assessment process 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 

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. 

We believe that the process by which 

determinations were made regarding the 

Tier 1 or non-Tier 1 status of the select 

agents and toxins was responsive to 

regulated community concerns received 

during the comment period for the 

advance notice of proposed rulemaking 

as well as for the proposed rule. 

One commenter asked why the 

requirements for working with plant 

pathogens had not been lessened. The 

commenter stated that a transparent 

process does not exist that is inclusive 

of expert opinion from both the private 

and public sectors to determine which 

agents should be removed or added to 

the list of select agents and toxins. 

We are making no changes as a result 

of this comment. In creating the Tier 1 

class of agents, the Select Agent 

Program considered and rejected the 

idea of designating the remaining agents 

as ‘‘Tier 2.’’ The aim of establishing the 

Tier 1 category is to account for and 

respond to the particular risks 

associated with the agents and toxins in 

this category by increasing their 

handling and security requirements 

accordingly. The establishment of the 

Tier 1 category is in no way intended to 

imply that the non-Tier 1 agents pose a 

lesser risk to public health and safety 

than they have previously. In 

accordance with that fact, we have not 

decreased the handling and security 

requirements for those non-Tier 1 

agents. Further, we determined that the 

establishment of more varying levels of 

risk would serve to create the need for 

increased administrative oversight and 

complication for regulated entities. We 

believe that the process by which these 

determinations were made was sensitive 

to public and expert opinion via the 

comment period on the initial advance 

notice of proposed rulemaking as well 

as on the proposed rule. 

Security Measures for Tier 1 Select 

Agents or Toxins 

We also proposed additions to the VS 

regulations that would allow for the 

optimization of security measures for 

those select agents or toxins that are 

designated as Tier 1. These 

requirements included: 

• Additions regarding the assessment 

of persons prior to their access to Tier 

1 select agents and toxins that would be 

made to the security plan currently 

required to be developed by all entities 

seeking approval for the possession, use, 

and transfer of select agents and toxins; 

ongoing oversight of those persons with 

access to Tier 1 select agents and toxins; 

and the role of the entity’s responsible 

official in coordinating and assuring the 

security of Tier 1 select agents and 

toxins; 

• Security enhancements that include 

provisions for security barriers, 

intrusion detection and monitoring, 


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delay/response force, access control, 

and information security; 

• Additions to the biosafety plan 

currently required to be developed by 

all entities seeking approval for the 

possession, use, and transfer of select 

agents and toxins that would describe 

implementation of an occupational 

health program for individuals with 

access to Tier 1 select agents and toxins; 

• Development of security policies 

and procedures describing the entity’s 

response to a failure of an intrusion 

detection or alarm system and 

notification procedures for the Federal 

Bureau of Investigation (FBI) in the 

event of theft or suspicious activity that 

may be criminal in nature involving a 

Tier 1 select agent or toxin. These 

policies and procedures would be 

required as part of the entity’s incident 

response plan; and 

• Required annual insider threat 

awareness briefings focused on how to 

identify and report suspicious 

behaviors. 

We have made changes to some of 

these proposed requirements, which are 

discussed in detail below. 

Many commenters had questions or 

concerns regarding the additions to the 

security plan for those entities 

possessing a Tier 1 select agent or toxin 

as proposed in 9 CFR 121.11(e). Specific 

issues addressed by the commenters 

included: Conduct of 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 

select agents and toxins. Commenters 

generally fell into two categories in their 

responses to the proposed additions: 

Some felt that the requirements were too 

vague to prove useful, creating 

administrative burden without 

improving the overall security of Tier 1 

select agents and toxins, while others 

felt that the requirements could or 

would require entities to behave in a 

manner contrary to local laws, privacy 

laws, or union contracts. 

For the most part, we anticipate that 

these requirements are already being 

met and that these regulations will 

merely require those entities possessing 

a Tier 1 select agent or toxin to codify 

and document the systems and 

processes currently in place. It should 

be noted 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 those 

recommendations given to the select 

agent program by the FESAP. As a 

matter of clarification, the select agent 

program considered the FESAP 

recommendations, as well as 

recommendations from other sources 

(e.g., National Science Advisory Board 

for Biosecurity), in developing the 

proposed rule and suitability 

assessment guidance documents; 

however, we are not adopting all of the 

specific recommendations found in 

these studies. While we have created 

specific guidance to aid in compliance 

with this section of the revised 

regulations, we are deliberately leaving 

the regulatory text in its broadly-written 

state in order to allow entities a measure 

of flexibility in how they meet the 

requirements. Given our experience 

with the select agent and toxin 

regulations and the wide variety of 

regulated entities the regulations cover, 

we have found this to be the most 

effective approach. The 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 this 

document include, but are not limited 

to: 

• Understanding the risks and 

reasons for suitability assessments; 

• Delineating the roles and 

responsibilities of individuals to ensure 

optimal security; 

• Requesting information about 

individuals in a standardized manner 

and assessing individuals in the context 

of safety and security; 

• Responding to reports in a 

consistent, prompt, and confidential 

manner; and 

• Providing training for recognizing 

and reporting suspicious behavior. 

Full guidance on this and other issues 

may be found on the National Select 

Agent Registry at www.selectagents.gov. 

In 9 CFR 121.11(e)(4)(i), we proposed 

that regulated entities with Tier 1 select 

agents and toxins prescribe and/or 

implement ‘‘procedures that limit access 

to registered space only to those 

approved by the HHS Secretary or the 

Administrator and meet the criteria of 

the entity’s program that will ensure 

individuals with access approval to 

select agents and toxins are trustworthy 

and behaving in a manner that upholds 

public health and safety, the protection 

of animal or plant health and animal or 

plant products, security, and the 

integrity of the scientific enterprise.’’ 

We are making a minor change to the 

proposed language in 9 CFR 121.11(e)(4) 

in order to stipulate that entities must 

implement these security 

enhancements, not merely prescribe 

and/or implement them. The proposed 

rule stated that ‘‘Entities with Tier 1 

select agents and toxins must prescribe 

and/or implement the following security 

enhancements.’’ We are removing the 

words ‘‘prescribe and/or’’ for the 

purposes of clarity. Our original intent 

in creating that provision was to require 

the use of the security enhancements in 

question by those entities with Tier 1 

select agents or toxins. By removing the 

words ‘‘prescribe and/or’’ we are 

eliminating a potential loophole by 

which entities may have been able to 

establish but not fulfill these 

requirements while remaining in 

compliance with the regulations. 

Regarding the proposed language in 9 

CFR 121.11(e)(4)(i), one commenter 

stated that the use of the phrase 

‘‘trustworthy and behaving in a manner 

that upholds public health and safety, 

the protection of animal or plant health 

and animal or plant products, security, 

and the integrity of the scientific 

enterprise’’ would establish a regulatory 

standard that would prove difficult or 

impossible to enforce due to its 

subjective nature. 

We agree with the commenter’s 

observation and have changed the 

language to require that entities 

possessing Tier 1 select agents or toxins 

prescribe and implement ‘‘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 believe that 

this establishes a more specific set of 

requirements for regulated entities. 

In 9 CFR 121.11(e)(4)(iv) we proposed 

that regulated entities with Tier 1 select 

agents and toxins establish a minimum 

of three barriers where each subsequent 

barrier is different and adds to the delay 

in reaching secured areas where select 

agents and toxins are used or stored. 

Barriers would be required to be 

monitored in such a way as to detect 

and assess intentional and unintentional 

circumventing of established access 

control measures under all conditions 

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

commenters requested clarification 

regarding what was meant by the term 

‘‘barrier’’ and asked for examples of 

what constitutes a barrier. The 

commenters suggested that a definition 

for ‘‘barrier’’ be added to the definitions 

sections in 7 CFR 331.1 and 9 CFR 

121.1. 

We agree with the commenters and 

we have added a definition for security 

barrier to read as follows: ‘‘A physical 

structure that is designed to prevent 

entry by unauthorized persons, animals, 

or materials.’’ In addition, we have 

altered the language concerning security 


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barriers in 9 CFR 121.11(f)(4)(iv) in 

order to clearly indicate that the final 

security barrier must limit access to the 

select agent or toxin to personnel 

approved by the HHS Secretary or 

Administrator and following a security 

risk assessment by the Attorney General. 

In 9 CFR 121.11(e)(4)(v), we proposed 

that all registered space and areas that 

reasonably afford access to the 

registered space must be protected by an 

intrusion detection system (IDS) unless 

physically occupied. One commenter 

stated that the proposed requirement 

contained a potential loophole by which 

an entity could argue that the presence 

of a janitor or similar personnel in 

registered space outside of normal 

working hours would allow that entity 

to avoid installation of an IDS. The 

commenter suggested that such a 

situation could be avoided by adding a 

stipulation that an IDS would need to be 

used when the entity was not 

‘‘physically occupied by the routine 

contingent of working, approved 

employees.’’ 

We disagree with the commenter’s 

observation as it is unlikely that the 

entity would be occupied at all hours, 

thus creating the loophole that would 

allow an entity to fail to install an IDS. 

We are also not adopting the 

commenter’s suggestion to add language 

regarding the presence of approved 

employees as we believe that would 

create confusion concerning the number 

of employees that could be described as 

‘‘the routine contingent.’’ Further, the 

IDS is one aspect of the security 

measures required for regulated entities. 

In the scenario proposed by the 

commenter, the IDS would not be 

engaged if a janitor or other personnel 

were present in the entity outside of 

normal working hours; however, the 

other required physical security 

measures would serve to protect the 

entity at that time. Finally, the training 

and employee suitability assessments 

required for those employees with 

access to select agents and toxins would 

also serve to ensure that those 

employees who work in registered areas 

understand and can employ the 

necessary security and safeguarding 

measures to maintain the physical 

security of the entity. 

In 9 CFR 121.11(e)(4)(vii), we 

proposed to require that entities provide 

backup power and energy sources to 

ensure that information security 

networks and integrated access controls 

and related systems will maintain 

power during emergencies. While we 

did not receive any comments on this 

issue, in response to comments received 

by CDC and in the interests of 

maintaining parity between the APHIS 

and HHS regulations, we are amending 

the text to stipulate that only those 

entities with powered access control 

systems will need to fulfill this 

requirement. We have also reworded the 

requirement to clarify that the aim is 

maintenance of physical security 

standards in the case of a power 

disruption and that this maintenance 

may, among the alternatives, take the 

form of backup power. 

In 9 CFR 121.11(e)(4)(viii) we 

proposed that response time for security 

forces or local police must not exceed 

15 minutes from the time of an intrusion 

alarm or report of a security incident for 

any entity with Tier 1 select agents and 

toxins. One commenter stated that such 

a requirement would be burdensome, 

unattainable, and cost-prohibitive 

depending upon the number and nature 

of the alarms. The commenter went on 

to state that the security system at their 

entity sounds an alarm when a door is 

held open longer than a preset length of 

time and that most alarms occur during 

working hours, primarily as the result of 

staff holding the door open too long. 

The commenter explained that requiring 

security respond to all these alarms is 

unwarranted, excessive, and costly. The 

commenter suggested that a better 

alternative would be for a laboratory 

supervisor or manager to be notified of 

and investigate these incidents, 

therefore allowing entities to respond in 

a manner commensurate with the 

severity of the incident that triggered 

the alarm. 

Our selection of the 15 minute 

response time is based on Department of 

Defense (DOD) and DHS standards for 

high value assets and also on our 

analysis of incident response plans 

provided by the regulated community 

since 2003. However, based on this 

comment and others received by CDC, 

we have modified the language in this 

section. We have retained the 15 minute 

response time goal for security forces or 

local police, but we have also provided 

additional flexibility for entities to 

develop systems in line with the 

optimal achievable response time in 

their area. Entities may either 

incorporate the 15 minute response time 

into their security plans or determine an 

alternate response time calculated in 

conjunction with security forces or local 

police. Response time can be 

determined many ways. For example, an 

entity can: 

• Enter into a formal agreement with 

local law enforcement. 

• Discuss with local law enforcement. 

• Discuss with the IDS service 

provider. 

• Conduct an exercise with the guard 

force. 

The issue of multiple false alarms and 

the potential costs associated with such 

a situation as raised by the commenter 

is more appropriately addressed at the 

entity level. 

In 9 CFR 121.11(e)(4)(ix) we proposed 

to require that entities conduct complete 

inventory audits of all Tier 1 select 

agents and toxins in long-term storage 

upon the physical relocation of a 

collection or inventory of select agents 

or toxins for those Tier 1 select agents 

or toxins in the collection or inventory, 

upon the departure or arrival of a 

principal investigator for those Tier 1 

select agents or toxins under the control 

of that principal investigator, or in the 

event of a theft or loss of a Tier 1 select 

agent or toxin. 

We have reevaluated this provision in 

light of comments received on the CDC 

rule and, based on our experience with 

the select agent program, we believe that 

this requirement needs to be applied to 

all select agents and toxins, and not 

only Tier 1 select agents and toxins. 

This change serves to codify our current 

policy concerning inventory audits. We 

have therefore revised the language to 

address inventory verification for all 

select agents and toxins. 

In the case of those entities which 

possess FMD and rinderpest virus, we 

proposed to require four barriers, 

including one barrier that is a perimeter 

security fence or equivalent. These 

requirements were listed in proposed 9 

CFR 121.11(e)(5)(i). One commenter 

inquired as to what the equivalent to a 

perimeter security fence would be. The 

commenter also wished to know if an 

IDS would be considered a barrier. 

One equivalent to a perimeter security 

fence would be a perimeter wall 

surrounding a specific building, 

complex, compound, or campus, with 

24 hour a day, 7 days a week 

monitoring. Such a wall would serve a 

purpose identical to a perimeter security 

fence. We have developed guidance to 

assist entities with the security barrier 

requirement, which covers the issue of 

perimeter fencing. Guidance documents 

may be found on National Select Agent 

Registry at www.selectagents.gov. As to 

the commenter’s question regarding the 

IDS: As stated above, a security barrier 

would include only natural or manmade obstacles preventing or delaying 

the movement of persons, animals, or 

materials. While an IDS may alert 

security or other personnel to potential 

incidents, the IDS itself would not be 

considered to be a security barrier since 

it does not actively create an obstacle or 

delay. 

Another commenter asked whether 

the proposed requirements would make 

it illegal for U.S. veterinary diagnostic 


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laboratories to perform diagnostic and/ 

or surveillance testing following an 

FMD outbreak on U.S. soil if the 

laboratories in question did not have a 

fourth security barrier. The commenter 

recommended that we revise the 

paragraph in order to clarify our intent. 

We are making no changes as a result 

of this comment. The select agent 

program recognizes the critical role of 

diagnostic laboratories in the early 

detection of and response to outbreaks 

of select agent and toxin-related disease 

in humans and agriculture. While all of 

the Tier 1 regulatory requirements will 

apply to entities that maintain 

permanent stocks of Tier 1 select agents 

and toxins, in the case of a public health 

or agricultural emergency, a diagnostic 

laboratory may request to retain the 

select agent or toxin under the 

provisions contained in 9 CFR 121.6(e). 

Two commenters recommended that 

the select agent program consult with 

administrators and laboratory managers 

from public and private research 

institutions prior to the development of 

any framework of suitability that can be 

used to address security concerns. 

We will engage subject matter experts 

as necessary in the development of 

guidance documents which may be 

found on the National Select Agent 

Registry at www.selectagents.gov. The 

select agent program welcomes feedback 

on the usability and usefulness of 

existing guidance documents at any 

time. 

One commenter suggested that the 

minimum security provisions for Tier 1 

select agents and toxins should include 

video monitoring of all select agents and 

toxins work and storage areas, a twoperson rule for entry into select agents 

and toxins work and storage areas, and 

psychological assessment and 

monitoring of those employees working 

with select agents and toxins. 

We are making no changes as a result 

of this comment. The specific measures 

the commenter suggested were 

considered and rejected in favor of the 

more general requirements listed. The 

select agent program is highly conscious 

of the need to balance biosecurity and 

biocontainment concerns with allowing 

entities the necessary flexibility so as to 

not impede their research unduly. Since 

there is variety in the type and size of 

entities covered under the regulations, 

we believe this approach is warranted. 

We would note that the regulations do 

not preclude any given entity from 

adopting the approach suggested by the 

commenter, among others. 

One commenter stated that, while 

many of the proposed security changes 

are already in place, some are not and 

it was unclear that additional costly or 

impractical security measures would 

provide any additional benefit since 

existing measures have proven adequate 

to protect the security of these agents. 

We are making no changes as a result 

of this comment. It was our 

determination, based on the information 

available to us, that the additional 

security requirements would not 

constitute an economic burden on the 

regulated entities. In many cases these 

regulations serve to codify systems and 

procedures already in use in these 

regulated entities. 

The regulations in 9 CFR 121.12 

concern the development of a biosafety 

plan that establishes measures sufficient 

to contain the select agent or toxin (e.g., 

physical structure and features of the 

entity, and operational and procedural 

safeguards). We proposed to add a 

paragraph that would stipulate that 

entities registered to possess Tier 1 

select agents or toxins establish an 

occupational health program for 

individuals with access to Tier 1 select 

agents and toxins. One commenter 

recommended that the occupational 

health program requirements be 

instituted for all select agents and 

toxins, regardless of their categorization. 

We are making no changes in 

response to this comment. Due to the 

greater level of concern associated with 

Tier 1 select agents and toxins the select 

agent program needs to ensure that 

entity safety protocols are in place. 

Further, after considering the issue and 

in light of the fact that it caused 

confusion amongst some commenters on 

the CDC proposed rule, we are 

eliminating the sentence that reads, 

‘‘The occupational health program may 

also be made available to individuals 

without access to Tier 1 select agents 

and toxins.’’ While we believe that 

regulated entities should use their 

discretion and judgment in considering 

whether the creation of an occupational 

health program applicable to those 

employees working with non-Tier 1 

select agents and toxins is needed, such 

a suggestion is not appropriately 

contained in the regulations. Guidance 

on the development of an occupational 

health program may be found on the 

National Select Agent Registry at 

www.selectagents.gov. 

The regulations in 9 CFR 121.15 

concern required mandatory training for 

staff and visitors who work in or visit 

areas where select agents or toxins are 

handled or stored. In 9 CFR 121.15(b), 

we proposed to add a requirement that 

entities with Tier 1 select agents and 

toxins must conduct annual insider 

threat awareness briefings on how to 

identify and report suspicious 

behaviors. One commenter stated that 

this training should be required for all 

registered entities possessing, storing, or 

transferring select agents, not just those 

with Tier 1 select agents or toxins. 

We are making no changes in 

response to this comment. Due to the 

greater level of concern associated with 

Tier 1 select agents and toxins the select 

agent program needs to ensure that 

entity safety protocols are in place. 

Regulated entities should use their 

discretion and judgment in considering 

whether the creation of an annual 

insider threat awareness training 

program applicable to those employees 

working with non-Tier 1 select agents 

and toxins is needed. Guidance on the 

development of annual insider threat 

awareness training may be found on the 

National Select Agent Registry at 

www.selectagents.gov. 

Another commenter asked for 

clarification and guidance regarding the 

requirement for annual insider threat 

awareness briefings. The commenter 

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. 

While we have created specific 

guidance regarding this section of the 

revised regulations, that guidance does 

not take the form of a prescriptive 

program with content that may then be 

adapted and distributed as the 

commenter requests. Given our 

experience with the select agent and 

toxin regulations and the wide variety of 

regulated 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 

documents will contain specific 

examples of best practices that we 

believe entities would be well served in 

adopting including, but not limited to, 

a designated person to manage the 

assessment of laboratory personnel, 

laboratorian involvement in threat 

migration, and those behaviors of 

concern which may indicate a possible 

insider threat. Full guidance on this and 

other issues may be found on the 

National Select Agent Registry at 

www.selectagents.gov. 

Miscellaneous Changes 

We proposed to make several smallerscale changes to the regulations, 

including the addition of definitions 

and clarification of language concerning 

security, training, biosafety, 

biocontainment, and incident response. 

These changes are intended to increase 

the usability of the select agent 


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regulations as well as provide for 

enhanced program oversight. 

In 7 CFR 331.1 and 9 CFR 121.1, we 

proposed to add definitions for 

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, and unlawful user of any 

controlled substance. These definitions, 

which described specific aspects of the 

proposed definition of restricted person, 

were intended to assist regulated 

entities as well as those seeking 

approval to access select agents and 

toxins to better understand what status 

or activities, past or present, might 

prohibit such access. 

Four commenters stated that these 

definitions needed to be further 

clarified. The commenters generally 

characterized the proposed definitions 

as either overly restrictive or vague. 

After careful consideration we have 

agreed with the commenters and have 

decided not to include these definitions 

or a definition for restricted person in 

the final rule. We will look to develop 

additional guidance in this area. 

We proposed to add a definition for 

recombinant and synthetic nucleic 

acids. This addition was deemed 

necessary, as the term ‘‘synthetic 

nucleic acids’’ is employed in the 

proposed changes to the select agent 

regulations. We proposed to include 

synthetic nucleic acids in the 

regulations because, while synthetic 

nucleic acids have the same potential 

for harm as recombinant nucleic acids, 

the process of production is different. 

One commenter stated that the 

proposed definition has implications in 

all areas currently impacted by 

synthetic biology technology, such as 

industrial enzymes, renewable 

chemicals for pharmaceutical and 

industrial applications, bio-based 

products, personal care products, 

renewable specialty chemicals, biofuels, 

and healthcare products. The 

commenter argued that consequences of 

adopting the proposed definition could 

impede the growth of sustainable 

products from emerging fields such as 

synthetic biology technology. The 

commenter therefore recommended that 

we not adopt the new definition of 

recombinant and synthetic nucleic acids 

as stated in the proposed rule, arguing 

that the existing language of the 

regulation is sufficient to cover the 

current uses of synthetic nucleic acids. 

The commenter further stated that the 

proposed definition utilizes language 

that was proposed to, but rejected by, 

the National Institutes of Health 

Recombinant DNA Advisory Committee 

(NIH–RAC). The commenter suggested 

that if the select agent program finds it 

necessary to introduce a new definition 

for recombinant and synthetic nucleic 

acids, that we follow the leadership of 

the NIH–RAC and establish a simpler 

definition that is not focused on the 

underlying mechanism of production of 

the nucleic acids. 

We disagree with the commenter’s 

assertion regarding the broad impact of 

the definitions used by the select agent 

program. Our scope of oversight is 

limited to the list of select agents and 

toxins and therefore does not extend to 

all synthetic biology. However, we do 

agree that any definition adopted for use 

in the regulations should be based on 

the most current information available 

from subject matter experts. Following 

extensive consultation with the NIH, we 

have updated the definition of 

recombinant and synthetic nucleic acids 

to reflect the most current thinking on 

the subject. In addition, we have 

separated the definition of recombinant 

nucleic acids from the definition of 

synthetic nucleic acids for purposes of 

clarity. 

We proposed to add a definition for 

occupational exposure to the VS 

regulations in 9 CFR 121.1 as it is used 

in the regulations but not defined. This 

definition was based on that used in the 

Occupational Safety and Health 

Administration regulations in 29 CFR 

1910.1030. We did not propose to add 

a corresponding definition to the PPQ 

regulations in 7 CFR 331.1 since PPQ 

select agents and toxins do not pose a 

severe threat to human health and, 

therefore, it is unnecessary to address 

personnel safety and health. One 

commenter suggested that we expand 

the definition to specify that, due to 

aerosol transmission, such exposure 

incidents may impact other employees 

working in the same area. 

We agree with the commenter that the 

proposed definition did not adequately 

address the possibility of aerosol 

transmission and have amended the 

language accordingly. 

Additionally, we are also removing 

references to rickettsiae in the 

definitions for biological agent and 

toxin. This change is necessary because 

there are no rickettsiae select agents or 

toxins regulated by APHIS on the list of 

select agents and toxins. 

We proposed to amend 7 CFR 

331.3(e), 9 CFR 121.3(e) and 9 CFR 

121.4(e). These paragraphs specify that 

attenuated strains of select agents or 

toxins may be excluded from the 

requirements of the select agent 

regulations subject to an official request 

and supporting scientific information. 

We proposed to state that the ‘‘inactive 

form of a select toxin’’ may be excluded 

from regulation under each respective 

part subject to the application 

procedure. We also proposed to update 

the Web site address in paragraph (e)(1) 

of each section as all information 

concerning the Select Agent Program is 

now centralized on the National Select 

Agent Registry at http:// 

www.selectagents.gov/. Finally, we 

proposed to remove the language stating 

that exclusions will be published in the 

Federal Register. At the time the 

regulations were initially created we 

anticipated publication of exclusions 

both in the Federal Register and on the 

Internet; however, we have found that 

publication on the National Select 

Agent Registry Web site only has served 

to provide the most up-to-date 

information to the regulated 

community. 

One commenter suggested that, in 

addition to publication of exclusions on 

the National Select Agent Registry Web 

site we should also develop and 

maintain an email distribution list so 

that registered facilities could be 

notified when updates are added to the 

Web site. 

We currently engage in the type of 

email updates that the commenter 

suggests. Emails are sent to responsible 

officials and alternate responsible 

officials at all registered entities. 

Dissemination of that information is at 

the discretion of the responsible 

officials and alternate responsible 

officials. We plan on issuing guidance 

and suggestions regarding information 

dissemination, which we believe will 

enable further information sharing 

within regulated entities. 

Another commenter asked that we 

add a timeline to the regulations 

indicating when the person requesting 

the exclusion should expect to receive 

a written response. The commenter 

stated that, in the case of grant 

applications, it may be difficult to meet 

deadlines if the applicant has no idea 

how long a response from the select 

agent program will take. 

We are making no changes as a result 

of this comment. Due to the wide 

variety of material submitted for 

consideration for exclusions, 

establishment of a timeline as the 

commenter recommends is impractical. 

The select agent program necessarily 

examines each application on a case-bycase basis. We strive to make the 

process as efficient as possible. 

The regulations in 9 CFR 121.6 set out 

guidelines for those instances where 

overlap select agents and toxins may be 

considered exempt from the regulations. 

Specifically, § 121.6(e) concerns 


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procedures by which an individual or 

entity may be exempted from the 

requirements of the regulations if 

necessary in order to respond to a 

domestic or foreign agricultural 

emergency involving an overlap select 

agent or toxin. Upon further 

consideration, in order to eliminate an 

unnecessary burden on such an 

individual or entity, we have removed 

the provision stating that the individual 

or entity must complete APHIS/CDC 

Form 5 in order to request such an 

exemption. Guidance on requesting an 

exemption for an individual or entity in 

the case of a domestic or foreign 

agricultural emergency involving an 

overlap select agent or toxin may be 

found on the National Select Agent 

Registry at www.selectagents.gov. 

The regulations in 7 CFR 331.9 and 9 

CFR 121.9 set out requirements for 

entities requesting to work with select 

agents and toxins to designate a 

responsible official, who ensures that 

the entity continues to meet the 

requirements of the regulations. We 

proposed to explicitly require that all 

designated responsible officials possess 

the appropriate training or expertise to 

execute their required duties. We also 

proposed to clarify the role of alternate 

responsible official in order to 

definitively establish that the alternate 

responsible official must have the 

knowledge and authority to act for the 

responsible official in his/her absence. 

Finally, we proposed to add a 

requirement that the responsible 

official’s principal duty station be the 

physical location of the registered 

entity. 

One commenter stated that the 

language concerning responsible 

officials is not clear and may cause 

institutions to unnecessarily create new 

administrative structures and positions 

to meet this requirement. The 

commenter urged the select agent 

program to work with research 

institutions in order to identify the most 

appropriate level of administration for 

the responsible official. 

We are making no change in response 

to this comment. The responsible 

official should be an individual who can 

perform all of the duties required for 

that position. The regulations were 

designed to place the responsibility for 

ensuring entity compliance with the 

regulations in one position. Given the 

wide variety of entities covered by the 

regulations, establishing more 

prescriptive guidelines would decrease 

the flexibility and usefulness of the 

regulations to those entities. We neither 

require nor prohibit the establishment of 

a separate administrative position for 

the responsible official as we leave it to 

the entity to decide how best to 

designate a responsible official who 

meets the requirements of the 

regulations. 

Another commenter said that the 

absence of specific requirements 

regarding responsible official 

qualifications will establish an 

inspection process that is subjective and 

ineffectual. The commenter asked that 

we add a section that explains and/or 

defines what we consider the 

‘‘appropriate training or expertise’’ 

necessary for an entity’s responsible 

official. 

We have established the regulations 

regarding the training and expertise of 

the responsible official in order that 

they provide maximum flexibility to 

regulated entities. The reasons for this 

are twofold: First, given the quickly 

developing and changing fields of 

biosafety and biosecurity, any attempt 

on our part to strictly define required 

training and expertise within the 

regulations would likely become 

obsolete as the parameters continue to 

evolve; second, given the wide variety 

of entities covered by the regulations, 

there is a need to maintain flexibility so 

that they may remain applicable to all 

of those entities. We have removed the 

reference to ‘‘appropriate training or 

expertise’’ and will continue to assess 

the performance of the responsible 

official based on his or her efficacy in 

implementing the regulatory 

requirements at his or her entity. With 

an eye to the non-specificity of the 

regulations, we have developed 

guidance documents regarding this and 

other aspects of entity compliance. They 

are available on the National Select 

Agent Registry at www.selectagents.gov. 

Five commenters requested further 

clarification regarding the proposed 

requirement that the responsible 

official’s principal duty station be the 

physical location of the registered 

entity. The commenters inquired 

whether this requirement would mean 

that the principal duty station should be 

in the same building or only at the same 

institution. 

In response to these comments and 

others received by the CDC, we are 

modifying the language in 7 CFR 331.9 

and 9 CFR 121.9 to stipulate that the 

responsible official must have a 

physical (as opposed to a telephonic or 

audio-visual link) presence at the 

registered entity to ensure that the entity 

is in compliance with the regulations. 

The responsible official will also be 

more quickly able to respond to any onsite incidents involving select agents 

and toxins if he or she is on-site. 

Three commenters asked that the 

definition of ‘‘entity’’ be clarified in 

relation to the requirement that the 

responsible official’s principal duty 

station be the physical location of the 

registered entity and the impact of the 

requirement assessed. The commenters’ 

request was based on their 

understanding that an entity has to be 

contiguous and that laboratories 

separated on a campus constitute 

separate entities. The commenters 

concluded that having separate 

responsible officials in this case would 

be burdensome. 

We realize that many entities are 

located on a campus with several 

registered laboratories in different 

buildings. The intent of this 

requirement is not to ensure that a 

responsible official is assigned to each 

physical laboratory but to ensure that 

the responsible official is physically 

located on the campus. 

We proposed to amend the 

regulations in 7 CFR 331.10 and 9 CFR 

121.10. These regulations establish 

parameters for restricting access to 

select agents and toxins and the process 

by which individuals may be approved 

for access to select agents and toxins 

after the completion of a security risk 

assessment by the Attorney General. 

Specifically, we proposed to add new 

provisions by which individuals may 

have access to select agents at entities 

other than the individual’s ‘‘home’’ 

entity. We also proposed to decrease the 

maximum length of time for which a 

security risk assessment will be valid 

from 5 years to 3 years in order to more 

expeditiously identify individuals who 

may have fallen into one of the 

prohibited or restricted categories. 

One commenter asked whether, 

during the time period in which an 

individual has access to select agents at 

entities other than the individual’s 

‘‘home’’ entity, that individual would 

have access to select agents at both 

facilities, or if the access approval 

would be transferred so that the 

individual would only have access to 

the select agents and toxins at the new 

entity for the time specified. The 

commenter stated that, from a biosafety 

and biosecurity perspective, limiting 

access to only one entity at the time 

would be appropriate. 

During this timeframe, the individual 

will maintain access to select agents at 

both facilities. We believe that such an 

arrangement will serve to facilitate 

collaboration between registered entities 

as well as enabling various entities to 

use their time and funds most efficiently 

in order to continue ongoing research. 

We do not agree with the commenter’s 

assertion that this procedure would 

threaten biosecurity or biosafety in any 

way since all registered entities are 


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required to undergo the same security 

screening process as established by the 

regulations. 

Two commenters stated that 

decreasing the maximum length of time 

for which a security risk assessment will 

be valid from 5 years to 3 years would 

represent an undue burden on registered 

entities. One commenter cited the 

generally low rate of turnover at these 

entities, while the other stated that the 

existing policy, with renewal every 5 

years, has proven to be both sufficient 

and cost effective since the 

establishment of the select agent 

regulations. The first commenter 

suggested that we allow for less frequent 

risk assessments in the case of those 

individuals working with non-Tier 1 

select agents and toxins only. The 

second commenter recommended 

making no changes to the 5-year 

interval. 

The decision to begin processing 

security risk assessments at 3-year 

rather than 5-year intervals was made as 

a result of the recommendations from a 

working group comprised, in part, of 

representatives from the DOD and the 

HHS as well as various subject matter 

experts. Based on input from the 

working group as well as the FBI, we 

have determined that conducting 

security risk assessment approvals every 

3 years is an effective method for 

increasing the security of our entities. 

Furthermore, the select agent program 

has been processing security risk 

assessments on a 3-year basis since June 

1, 2011. Since that date, we have not 

received any comments from the 

regulated community regarding 

additional financial or administrative 

burden associated with the changed 

practice. Regarding the first 

commenter’s suggestion to process 

security risk assessments differently for 

those individuals working with nonTier 1 select agents and toxins only, the 

establishment of the Tier 1 category is 

in no way intended to imply that the 

non-Tier 1 agents pose a lesser risk to 

public health and safety than they have 

previously. In accordance with that fact, 

we have not decreased the handling and 

security requirements for those non-Tier 

1 agents. 

We proposed to require that the 

security plan described in 7 CFR 331.11 

and 9 CFR 121.11 that must be 

developed by all registered entities be 

submitted for initial registration, 

renewals of registration, and at any 

other time upon request to replace the 

existing requirement that they be 

provided upon request only. We also 

proposed that the security plan contain 

provisions for the control of access to 

select agents and toxins, including the 

safeguarding of animals or plants 

intentionally or accidentally exposed to 

or infected with a select agent, against 

unauthorized access, theft, loss or 

release. We also proposed to add a 

requirement that the security plan 

include procedures that require the 

responsible official to immediately 

notify the FBI in order to initiate a 

threat assessment process in the event 

that he or she becomes aware of 

suspicious activity which is criminal in 

nature, related to the facility, its 

personnel, or select agents. We also 

proposed to add provisions for 

information security, including the need 

for backup measures if the entity relies 

on information systems for security. We 

also proposed to codify current 

practices for shipping, receiving, and 

storage of select agents and toxins to 

ensure that the entity has documented 

processes for securing and monitoring 

the shipment, receipt, and storage of 

these items. Finally, we proposed to 

amend paragraph (e) in 7 CFR 331.11 

and 9 CFR 121.11, which previously 

directed individuals creating a security 

plan to guidance for developing such 

documents contained in the ‘‘Morbidity 

and Mortality Weekly Report’’ from 

December 2002. We proposed that 

applicants would instead be directed to 

the ‘‘Security Information Document’’ 

and the ‘‘Security Plan Template’’ on 

the National Select Agent Registry Web 

site. 

Two commenters requested 

clarification concerning the proposed 

requirement that entities address 

procedures concerning animals or 

plants accidentally or intentionally 

exposed to or infected with a select 

agent. Specifically, the commenters 

requested clarification as to whether the 

requirement would be limited to 

experimental plants and animals that 

are possessed and controlled by the 

registered entity. One commenter 

suggested two additions to the 

requirements: One stipulating that the 

incident response plan only cover those 

animals or plants possessed and 

controlled by the entity and the second 

a certifying statement confirming that 

the State animal health official (or plantassociated equivalent) has an incident 

response plan in place to address 

intentional or accidental exposure to 

select agents for animals or plants 

throughout the State, including those 

plants or animals that are not possessed 

or controlled by the entity but may be 

located on the premises (e.g., wild 

animals). 

We are making no changes based on 

these comments. It was always our 

intent that the entity’s incident response 

plan be limited to those exposed plants 

and animals that are possessed by and 

controlled by the registered entity. 

One commenter suggested that we 

alter the wording from a requirement to 

safeguard animals or plants 

‘‘intentionally or accidentally exposed 

to or infected with a select agent’’ to a 

requirement to safeguard animals or 

plants ‘‘intentionally exposed to, or 

infected with, select agents.’’ The 

commenter stated that the suggested 

language would be clearer. 

We are making no changes based on 

this comment. We believe that animals 

or plants accidentally exposed to or 

infected with a select agent should be 

handled as select agents and 

safeguarded in the same manner as an 

animal or plant intentionally exposed to 

a select agent. 

In the preamble to the proposed rule, 

we stated that we were not proposing to 

require the security plan to address 

animals and plants exposed to select 

toxins. This is because recovering the 

toxin from within an animal or plant 

subject is highly difficult and such 

removal does not produce a reasonable 

yield of recovery. In addition, there is 

uncertainty as to whether or not the 

toxin would remain active when 

recovered from the animal or plant. For 

these reasons it is highly unlikely that 

once introduced into an animal or plant, 

a sufficient amount of toxin could be 

recovered to pose a significant hazard to 

public health, agriculture, or agriculture 

products. One commenter questioned 

that rationale, stating that while toxins 

are unlikely to be amplified or move 

into multiple hosts outside a given 

facility, there is still concern that 

amplification of toxins could occur in 

animals or insects during the course of 

an experiment. 

We disagree with the commenter’s 

assertion. Select toxins do not amplify 

the way select agents do. Toxins in an 

animal or insect would prove deadly to 

that organism before it could reach a 

level at which extraction would become 

possible. 

One commenter stated that our 

proposal to add a requirement that the 

security plan include procedures for the 

responsible official to 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 

contradicts guidance contained in the 

Nationwide Suspicious Activity 

Reporting (SAR) Initiative (NSI) 

established by the Department of 

Justice, creates a conflict within those 

entities that have their own recognized 

law enforcement agencies, and 

unnecessarily adds confusion due to the 

potential for concurrent jurisdiction. 

Two other commenters questioned the 


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rationale for requiring FBI reporting 

given that the select agent program is 

jointly administered by APHIS and CDC 

and, in the past, security concerns were 

directed to those agencies. 

We do not believe that there exists 

any conflict between the security 

requirements in 7 CFR 331.11 and 9 

CFR 121.11 and the guidance offered by 

the NSI. The intent of this requirement 

is to facilitate the involvement of 

antiterrorism resources which will 

increase the security of select agents and 

toxins. FBI field offices, which are 

centrally located in major metropolitan 

areas across the United States, can assist 

entities by working closely with them 

on crime threats. However, we agree 

with the commenters that it may be 

appropriate that notification of 

suspicious activity first be given to local 

law enforcement. We have therefore 

changed the language in 7 CFR 

331.11(c)(8) and 9 CFR 121.11(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.’’ 

Another commenter suggested that we 

require FBI notification for any 

suspicious activity involving select 

agents or toxins and not just activity 

that may be criminal in nature. The 

commenter argued that it is more 

appropriate for the FBI to determine 

whether or not the activity in question 

is criminal in nature. 

We are making no changes in 

response to this comment. The intent of 

this section of the regulations is to avoid 

excessive reporting to the FBI. It is our 

belief that a reasonable person would be 

able to determine if the behavior in 

question constitutes a potential criminal 

act, which would therefore necessitate 

FBI reporting. 

One commenter requested that we 

provide further details concerning the 

proposed requirements for additions to 

the security plan, specifically as it 

relates to information security. 

The purpose of the requirement in 

question is to clarify the language in 7 

CFR 331.11(c)(9)(i) and 9 CFR 

121.11(c)(9)(i) of the regulations that 

requires the entity to have procedures in 

place for information systems control. 

This is an overarching requirement that 

covers electronic and non-electronic 

information oversight by the regulated 

community. Our intent is not to regulate 

experimental data or the results of 

studies involving select agents and 

toxins but to regulate 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 

only be for access to the entity’s 

registered space and records pertaining 

to select agents and toxins, as identified 

in sections 7 CFR 331.11, 9 CFR 121.11, 

7 CFR 331.17, and 9 CFR 121.17. 

Another commenter stated that the 

information security requirement 

represents an added regulatory burden, 

and the impact of this requirement 

should be evaluated. 

For the most part, we anticipate that 

these requirements are already being 

met and will merely require entities to 

codify and 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 commenter. Issues 

addressed in this 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. Full 

guidance on information security may 

be found on the National Select Agent 

Registry at www.selectagents.gov. 

Another commenter said that the 

proposed requirement that authorized 

and authenticated users only be 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 their 

access be modified when the user’s roles 

and responsibilities change or when 

their access to select agents and toxins 

is suspended or revoked, would require 

registration and security risk 

assessments for all staff managing 

records pertaining to select agent work. 

The commenter argued that this 

requirement would increase the burden 

on manufacturers and institutions who 

utilize administrative or information 

technology staff for such document 

management. 

The security requirements referenced 

by the commenter refer only to those 

persons who have either physical access 

to select agents and toxins or who have 

the capability to alter security access to 

select agents and toxins. Guidelines 

concerning security requirements such 

as these may be found on the National 

Select Agent Registry at 

www.selectagents.gov. 

Another commenter stated that the 

meaning of the phrases ‘‘network 

connectivity monitoring’’ and ‘‘backup 

security measures in the event that 

access control systems and/or 

surveillance devices are rendered 

inoperable’’ should be clarified. 

Again, we note that, further details 

regarding these and other aspects of the 

information security requirements may 

be found in the guidance documents 

mentioned above, which may be found 

on the National Select Agent Registry at 

www.selectagents.gov. 

We proposed to require that an 

entity’s security plan 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 would provide that an entity 

must properly secure containers on site 

and have a written contingency plan for 

unexpected shipments. One commenter 

requested clarification regarding the 

meaning of the term ‘‘unexpected 

shipments.’’ 

We believe that the term ‘‘unexpected 

shipments’’ is self-explanatory and 

believe that the security plan should 

contain procedures for these handling 

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). 

The regulations in 7 CFR 331.13 and 

9 CFR 121.13 concern restricted 

experiments, which are those 

experiments that may not be performed 

by regulated entities without the 

approval of the Administrator. In 

addition to the existing prohibition on 

conducting restricted experiments, we 

proposed to state that entities would not 

be authorized to possess the products of 

restricted experiments without the 

approval of the Administrator. 

We also proposed 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 use of 

the drug to control 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 

DNA. We proposed this change because, 

while the introduction of a drug 

resistance trait would normally 

eliminate that drug as a therapeutic 

option to control the disease, there may 

be alternative drugs available to control 

the disease. 

In addition, we are adding a reference 

to ‘‘chemical resistance traits,’’ to the 

PPQ regulations in 7 CFR 331.13 in 

order to capture the potential transfer of, 


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or selection for, such traits that could 

adversely affect plant and agricultural 

health. Chemical resistant traits include, 

but are not limited to herbicide 

resistance, fungicide resistance, and 

pesticide resistance. We did not propose 

to add a corresponding definition to the 

VS regulations in 9 CFR 121.13 since 

chemical resistance traits are exclusive 

to plant biology. It should be noted that 

restricted experiments are not 

prohibited experiments; 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 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 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 may be advised regarding 

whether the experiment would be 

considered a restricted experiment and 

therefore require approval prior to its 

initiation. 

Two commenters were concerned 

about the proposed revisions classifying 

those experiments that introduce drug 

resistance to a select agent as restricted. 

The commenters suggested aligning the 

language concerning restricted 

experiments with the recombinant DNA 

guidelines issued by the NIH, which 

restrict and require approval only for 

those experiments with pathogens 

involving drug resistance for 

therapeutically useful agents against 

that pathogen. The commenters stated 

that the proposed language was too 

broad. 

We made no changes as a result of 

these comments. Contrary to the 

commenters’ assertion, we have not 

expanded the definition of a restricted 

experiment to include all experiments 

utilizing select agents or toxins with 

drug resistant traits, but only to those 

utilizing select agents or toxins with 

resistance to those drugs used to control 

disease in humans, veterinary medicine, 

or agriculture. The definition of a 

restricted experiment contained in the 

regulations is already aligned with the 

NIH recombinant DNA guidelines. 

One commenter argued that antibiotic 

resistance not previously present could 

emerge in one or more select agents at 

any time. The commenter wished to 

know if the possession of such a 

previously unknown antibiotic resistant 

select agent would mean that all such 

organisms would be required to be 

destroyed. The commenter expressed 

concern that such a requirement might 

inadvertently prevent research in the 

case of a select agent that suddenly 

developed new antibiotic resistance 

traits. 

We are making no changes to the 

regulations as a result of this comment. 

Regardless of whether the select agent 

develops a new trait, it is still 

considered and treated as a select agent 

from a biosafety or biocontainment 

perspective. The aspect of the process 

that makes a select agent the subject of 

a restricted experiment is the purposeful 

generation of antibiotic resistant 

properties. If a select agent developed 

new antibiotic resistance spontaneously, 

then it would be included in the 

category of select agents considered 

‘‘known to acquire the resistance 

naturally’’ as specified in 7 CFR 

331.13(a)(1) and 9 CFR 121.13(b)(1). 

Another commenter wanted to know 

whether the use of the terms ‘‘the select 

agent program’’ and ‘‘the 

Administrator,’’ which refer to two 

different entities, indicates that 

restricted experiments would require 

the approval of both the select agent 

program and the Administrator. 

Terms in this context are 

interchangeable, as the APHIS 

Administrator has delegated authority 

for establishing and enforcing the 

regulations to the select agent program. 

Approval is therefore only needed from 

the select agent program. 

Another commenter stated that an 

ombudsman, in the form of additional 

working groups, should be included in 

the approval process for restricted 

experiments. The commenter said that 

involvement of such groups in this 

capacity would serve to engage those 

regulated scientists while furthering 

their understanding of the select agent 

program. 

We are making no changes as a result 

of this comment. In reviewing 

applications to conduct restricted 

experiments, the select agent program 

utilizes the expertise of the 

Intragovernmental Select Agents and 

Toxins Technical Advisory Committee 

(ISATTAC), which is composed of 

Federal scientists from the CDC, NIH, 

FDA, APHIS, the Agricultural Research 

Service (ARS), APHIS’ Center for 

Veterinary Biologics (CVB), and DOD, 

and its USDA counterpart, the 

Agricultural ISATTAC, which is 

composed of Federal scientists from 

ARS, APHIS, and CVB. In the past, 

when appropriate, we have engaged the 

advice of subject matter experts from 

outside the government. 

The regulations in 7 CFR 331.14 and 

9 CFR 121.14 concern development of 

an entity’s incident response plan. We 

proposed to specify that each incident 

response plan be based upon a sitespecific risk assessment. We also 

proposed that the incident response 

procedures contain stipulations 

concerning animals and plants 

accidentally or intentionally exposed to 

or infected with a select agent. 

One commenter argued that the 

requirements in 7 CFR 331.14(a) and 9 

CFR 121.14(a), which stipulate that 

regulated entities must develop and 

implement a written incident response 

plan based on a site-specific risk 

assessment, are misleading. The 

commenter stated that, since there is no 

standard methodology for conducting 

such risk assessments, the addition of 

specific issues that must be addressed 

by a risk assessment should be included 

in order to provide additional guidance 

for the regulated community. The 

commenter further observed that, in 

general, the risk assessment 

requirements for agricultural select 

agents and toxins are somewhat 

different from those for human select 

agents and toxins. The commenter 

concluded that a one size fits all 

approach may be overly burdensome or 

scientifically inaccurate. 

We are making no changes based on 

this comment. The site-specific risk 

assessments required by the regulations 

in 7 CFR 331.14(a) and 9 CFR 121.14(a) 

are necessary in order to ensure the 

physical security of regulated entities. 

The risks cited by the commenter are 

matters of the biological risk presented 

by various select agents and toxins, 

which is a separate issue from the 

physical security of these select agents 

and toxins. The regulations are intended 

to prevent the theft, loss, or release of 

select agents and toxins. We also 

disagree with the commenter’s assertion 

that there is no standard methodology 

for conducting site-specific risk 

assessments. We have developed 

guidance on this subject that may be 

found on the National Select Agent 

Registry at www.selectagents.gov. 

We proposed to amend the 

regulations in 7 CFR 331.15 and 9 CFR 

121.15, which concern provision of 

mandatory training for staff and visitors 

who work in or visit areas where select 

agents or toxins are handled or stored. 

We proposed to require all registered 

entities to provide security awareness 

and incident response training. We also 

proposed to establish that training for 

escorted personnel would be based on 


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the risk associated with accessing areas 

where select agents and toxins are used 

and/or stored. We further proposed to 

require that refresher training, currently 

required on an annual basis, also be 

provided if a registered entity’s security, 

incident response, biosafety, or 

biocontainment plans are substantively 

altered. Finally, we proposed to specify 

that the responsible official ensure 

maintenance of training records. 

Currently there is no particular person 

designated as the entity’s required 

recordkeeper, only that a training record 

must be kept. 

One commenter suggested that 7 CFR 

331.15(a) should specify that 

information and training on both 

biocontainment and biosafety be 

provided, as only information and 

training on biosafety had been specified 

in the proposed rule. 

We agree with the commenter and 

have amended 7 CFR 331.15(a) in order 

to reflect the proper terminology in 

dealing with plant pathogens. 

We proposed that the regulations in 7 

CFR 331.15(a)(ii) concerning escorted 

personnel stipulate that training for 

such individuals must be based on the 

risk associated with accessing areas 

where select agents and toxins are used 

and/or stored. One commenter inquired 

what would represent an ‘‘appropriate 

level of training.’’ The commenter 

further wished to know how an entity 

would determine the risk associated 

with accessing such areas. Finally, the 

commenter asserted that there should be 

no need for non-approved individuals to 

potentially access areas where select 

agents and toxins are used and/or stored 

given that unsecured select agents or 

toxins could be moved elsewhere prior 

to the arrival of any escorted personnel. 

We disagree with the commenter’s 

assertion that non-approved individuals 

would never need to access areas where 

select agents and toxins are used and/ 

or stored. For example, there may be a 

need for the repair of a refrigeration unit 

in a laboratory where employees are 

utilizing select agents or toxins as a part 

of concurrent research work. In 

addition, inventories of select agents 

and toxins may be large enough to make 

moving them impractical and overly 

time-consuming. It is therefore 

necessary for any visitors to know and 

understand the biological risks 

associated with the select agents or 

toxins used and/or stored in the area to 

which they will have access. This 

training would necessarily vary 

depending upon the areas that the 

escorted personnel would need to 

access, which would be determined by 

the entity. Visitors should ideally be 

made aware of the safety and security 

procedures as defined by the entity in 

question; however, we are leaving the 

regulations in their broadly written state 

in order to provide the greatest amount 

of flexibility for the wide variety of 

entities subject to the requirements. 

We proposed to amend the 

regulations in 7 CFR 331.16 and 9 CFR 

121.16, which concern the transfer of 

select agents and toxins from one 

registered entity to another, in order to 

codify practices for shipping, receiving, 

and storage of select agents and toxins 

to ensure that all registered entities have 

documented processes for securing and 

monitoring the shipment, receipt, and 

storage of select agents and toxins that 

make it extremely unlikely that such 

materials would be made available to an 

unauthorized individual. 

Two commenters asserted that the 

provisions concerning transfer are 

unclear with regard to the subject of the 

transfer of materials covered by the 

exemptions for diagnostic or clinical 

laboratories under 7 CFR 331.5, 9 CFR 

121.5, and 9 CFR 121.6. The 

commenters requested that we clearly 

establish whether the new requirements 

supersede the existing provisions for 

transfer by exempt entities. 

We are making no changes as a result 

of this comment. Those materials which 

qualify for exemption from the 

regulations have always been 

considered separately from the rest of 

the listed select agents or toxins. This 

may be a result of the exemptions 

granted for diagnostic or clinical 

laboratories, a result of a specific 

exemption request, or for other reasons 

which may be found in 7 CFR 331.5, 9 

CFR 121.5, and 9 CFR 121.6. As a result, 

these materials are not subject to the 

regulations, including those portions of 

the regulations concerning transfers, 

apart from those sections pertaining to 

exemptions. 

However, given that some 

commenters on the CDC proposed rule 

expressed confusion associated with the 

proposed provision, we have revised the 

language in order to clarify our original 

intent. Packaging of select agents and 

toxins for transfer must be made by an 

APHIS or CDC-approved individual. 

The regulations in 7 CFR 331.17 and 

9 CFR 121.17 concern required 

recordkeeping procedures for regulated 

entities as those records relate to select 

agents and toxins. We proposed to add 

language to address synthetic select 

agent organisms and animals and plants 

inoculated with select agents. We also 

proposed to add recordkeeping 

requirements whereby regulated entities 

maintain an accurate, current inventory 

of any animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent (including number and 

species, location, and appropriate 

disposition). As previously stated, we 

did not propose to require regulated 

entities to keep records regarding 

animals or plants exposed to select 

toxins. 

Four commenters argued that 

counting individual vials of replicating 

biological agents is costly, burdensome, 

and a major source of frustration for 

investigators. The commenters went on 

to say that the requirement to measure 

volumes within each vial is problematic 

given both the ease with which volumes 

can change through natural processes 

and the difficulty in correctly assessing 

them in the frozen state during 

inventory verifications. The commenters 

stated that both counting vials and 

measuring volumes of individual vials 

are not effective means of increasing 

security. 

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 in 

establishing the 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 

maintaining accurate inventories of 

materials in long term storage, we have 

developed guidance that may be found 

on the National Select Agent Registry 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. 

Another commenter stated that there 

is concern that the additional 

requirements for inventory each time a 

select agent is moved will adversely 

impact the viability and quality of the 

material in question. 

We are making no changes as a result 

of this comment. In the case of those 

select agents and toxins in long-term 


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storage, collections of vials of materials 

can be recorded and grouped into 

tamper-evident containers and audits 

made of intact containers rather than 

audits of individual vials. This practice 

is stipulated in the current guidance 

document regarding long term storage, 

which is available on the National 

Select Agent Registry at 

www.selectagents.gov. Those select 

agents and toxins that are part of an 

entity’s working stock are already in 

regular use and we therefore do not 

anticipate adverse effects arising from 

any required accounting. 

Based on comments received on the 

CDC rule, we now recognize that there 

has been some confusion between those 

animals (including arthropods) and 

plants considered to be ‘‘working stock’’ 

and those considered to be ‘‘inventory.’’ 

To that end, we have developed 

guidance that will enable entities to 

better differentiate between these two 

categories. This guidance is available at 

www.selectagents.gov. It was not our 

intent to require a formal inventory of 

animals or plants intentionally or 

accidentally exposed to or infected with 

a select agent, but merely to state that 

entities should keep some record of 

such animals or plants. In order to 

clarify our intent regarding ‘‘working 

stock’’ and ‘‘inventory,’’ we are revising 

7 CFR 331.17(a)(2) and 9 CFR 

121.17(a)(2) 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. 

Indirect and Economic Consequences 

Eight 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 

agents and toxins will mandate more 

Federal oversight and institutional 

compliance requirements, resulting in 

increased costs to taxpayers both 

directly and indirectly through reduced 

research efficiency. Commenters 

requested that the full economic 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 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 select 

agent program is to ensure the 

appropriate availability of biological 

agents and toxins for research, 

education, and other legitimate 

purposes. To achieve both requires 

balancing the need for continuing 

biological research with requiring a 

level of safety and security 

commensurate with the risks posed by 

these select 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. We are, 

however, also aware that a lack of 

adequate safety and security 

requirements could result in damages 

measured not only in dollars but in 

human lives. It is our determination, 

based on the information available to us, 

that the additional requirements would, 

in many cases, codify systems and 

procedures already in use by a majority 

of regulated entities. 

We are also renumbering several 

sections of the PPQ regulations so that 

they will match the numbering of the 

VS regulations, which we believe may 

be useful for those entities housing both 

PPQ select agents and toxins and VS 

select agents and toxins. As proposed, 

the section numbering did not match up 

because we did not propose to classify 

any PPQ select agents and toxins as Tier 

1, so there were sections being added to 

the VS regulations that were not 

included in the PPQ regulations. 

Effective Date 

In response to comments received by 

the CDC requesting guidance and a 

timetable of when the proposed changes 

would need to be addressed, 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 ‘‘Dates’’ portion of this 

document, 60 days from the publication 

of the final rule, entities will be required 

to be in compliance with 7 CFR 331.1 

through 331.10, 331.13, and 331.16 

through 331.20 and 9 CFR 121.1 through 

121.10, 121.13, 121.16, 121.17, and 

121.20. One hundred and eighty days 

after the publication of the final rule, 

entities will be required to be in 

compliance with 7 CFR 331.11, 331.12, 

331.14, and 331.15 and 9 CFR 121.11, 

121.12, 121.13, 121.14, and 121.15. 

The staggered effective dates for the 

provisions of the final rule are based on 

the effective dates previously used for a 

final rule published by the Select Agent 

Program on March 18, 2005 (70 FR 

13242–13292, Docket No. 02–088–4). If 

the regulated community has concerns 

about the established timeline, they can 

contact the Federal select agent program 

for technical assistance. 

Therefore, for the reasons given in the 

proposed rule and in this document, we 

are adopting the proposed rule as a final 

rule, with the changes discussed in this 

document. 

Executive Orders 12866 and 13563 and 

Regulatory Flexibility Act 

This final rule has been determined to 

be significant/economically significant 

for the purposes of Executive Order 

12866 and, therefore, has been reviewed 

by the Office of Management and 

Budget. 

We have prepared an economic 

analysis for this rule. The economic 

analysis provides a cost-benefit analysis, 

as required by Executive Orders 12866 

and 13563, which 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, and equity). Executive Order 

13563 emphasizes the importance of 

quantifying both costs and benefits, of 

reducing costs, of harmonizing rules, 

and of promoting flexibility. The 

economic analysis also provides a final 

regulatory flexibility analysis 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 the Regulations.gov Web 

site (see footnote 1 in this document for 

a link to Regulations.gov) or by 

contacting the person listed under FOR

FURTHER INFORMATION CONTACT. 

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 rule, 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 


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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 rule 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. While the 

total cost of implementing the 

regulations is estimated to range 

between $2.8 million–$4.4 million 

across all entities with a Tier 1 agent or 

toxin and approximately $2.4 million in 

annual cost across all registered entities 

and the Federal Government, we believe 

many of these costs are currently 

incurred by affected entities as generally 

recognized practices. 

Executive Order 12372 

This program/activity is listed in the 

Catalog of Federal Domestic Assistance 

under No. 10.025 and is subject to 

Executive Order 12372, which requires 

intergovernmental consultation with 

State and local officials. (See 7 CFR part 

3015, subpart V.) 

Executive Order 12988 

This final rule has been reviewed 

under Executive Order 12988, Civil 

Justice Reform. This rule: (1) Preempts 

all State and local laws and regulations 

that are inconsistent with this rule; (2) 

has no retroactive effect; and (3) does 

not require administrative proceedings 

before parties may file suit in court 

challenging this rule. 

Executive Order 13175 

This rule has been reviewed in 

accordance with the requirements of 

Executive Order 13175, Consultation 

and Coordination with Indian Tribal 

Governments. The review reveals that 

this regulation will not have substantial 

and direct effects on Tribal governments 

and will not have significant Tribal 

implications. 

Paperwork Reduction Act 

In accordance with section 3507(d) of 

the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501 et seq.), the information 

collection or recordkeeping 

requirements included in this final rule 

have been submitted for approval to the 

Office of Management and Budget 

(OMB). When OMB notifies us of its 

decision, we will publish a document in 

the Federal Register providing notice of 

the assigned OMB control numbers or, 

if approval is denied, providing notice 

of what action we plan to take. 

E-Government Act Compliance 

The Animal and Plant Health 

Inspection Service is committed to 

compliance with the E-Government Act 

to promote the use of the Internet and 

other information technologies, to 

provide increased opportunities for 

citizen access to Government 

information and services, and for other 

purposes. For information pertinent to 

E-Government Act compliance related 

to this rule, please contact Mrs. Celeste 

Sickles, APHIS’ Information Collection 

Coordinator, at (301) 851–2908. 

List of Subjects 

7 CFR Part 331 

Agricultural research, Laboratories, 

Plant diseases and pests, Reporting and 

recordkeeping requirements. 

9 CFR Part 121 

Agricultural research, Animal 

diseases, Laboratories, Medical research, 

Reporting and recordkeeping 

requirements. 

Accordingly, we are amending 7 CFR 

part 331 and 9 CFR part 121 as follows: 

Title 7 

PART 331—POSSESSION, USE, AND 

TRANSFER OF SELECT AGENTS AND 

TOXINS 

■ 1. The authority citation for part 331 

continues to read as follows: 

Authority: 7 U.S.C. 8401; 7 CFR 2.22, 2.80, 

and 371.3. 

■ 2. Section 331.1 is amended as 

follows: 

■ a. In the introductory text of the 

definition of biological agent, by 

removing the word ‘‘rickettsiae,’’; 

■ b. By adding, in alphabetical order, 

definitions of information security, 

recombinant nucleic acids, security 

barrier, and synthetic nucleic acids; and 

■ c. In the introductory text of the 

definition of toxin, by removing the 

word ‘‘rickettsiae,’’. 

The additions read as follows: 

§ 331.1 Definitions. 

* * * * * 

Information security. Protecting 

information and information systems 

from unauthorized access, use, 

disclosure, disruption, modification, or 

destruction in order to provide: 

(1) Integrity, which means guarding 

against improper information 

modification or destruction, and 

includes ensuring information 

authenticity; 

(2) Confidentiality, which means 

preserving authorized restrictions on 

access and disclosure, including means 


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for protecting personal privacy and 

proprietary information; and 

(3) Availability, which means 

ensuring timely and reliable access to 

and use of information. 

* * * * * 

Recombinant nucleic acids. (1) 

Molecules that are constructed by 

joining nucleic acid molecules and that 

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

recombinant nucleic acids); or 

(2) Molecules that result from the 

replication of those described in 

paragraph (1) of this definition. 

* * * * * 

Security barrier. A physical structure 

that is designed to prevent entry by 

unauthorized persons, animals, or 

materials. 

* * * * * 

Synthetic nucleic acids. (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. 

* * * * * 

■ 3. Section 331.3 is amended as 

follows: 

■ a. By revising paragraph (b); 

■ b. In paragraph (c) introductory text, 

by adding the words ‘‘and/or synthetic’’ 

after the word ‘‘recombinant’’ each time 

it appears. 

■ c. In paragraph (c)(2) introductory 

text, by adding the words ‘‘and/or 

synthetic’’ after the word 

‘‘Recombinant’’. 

■ d. By adding paragraph (d)(3); and 

■ e. By revising paragraph (e) 

The revisions and addition read as 

follows:. 

§ 331.3 PPQ select agents and toxins. 

* * * * * 

(b) PPQ select agents and toxins: 

Peronosclerospora philippinensis 

(Peronosclerospora sacchari); Phoma 

glycinicola (formerly Pyrenochaeta 

glycines); Ralstonia solanacearum; 

Rathayibacter toxicus; Sclerophthora 

rayssiae; Synchytrium endobioticum; 

Xanthomonas oryzae. 

* * * * * 

(d) * * * 

(3) Any subspecies of Ralstonia 

solanacearum except race 3, biovar 2 

and all subspecies of Sclerophthora 

rayssiae except var. zeae, 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 Administrator that 

the attenuated strain or inactivated 

toxin does not pose a severe threat to 

plant health or plant 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. 

* * * * * 

■ 4. Section 331.9 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); 

■ d. By revising the first sentence of 

paragraph (b) 

The addition and revision read as 

follows:. 

§ 331.9 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. 

* * * 

* * * * * 

■ 5. Section 331.10 is amended as 

follows: 

■ a. By redesignating paragraphs (e) 

through (i) as paragraphs (f) through (j) 

respectively; 

■ b. By adding a new paragraph (e); and 

■ c. In newly redesignated paragraph (i), 

by removing the number ‘‘5’’ and adding 

the number ‘‘3’’ in its place. 

The addition reads as follows: 

§ 331.10 Restricting access to select 

agents and toxins; security risk 

assessments. 

* * * * * 

(e) A person with valid approval from 

the HHS Secretary or Administrator to 

have access to select agents or 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. 

* * * * * 

■ 6. Section 331.11 is amended as 

follows: 

■ a. By revising paragraph (b); 

■ b. By revising paragraph (c)(2); 

■ c. In paragraph (c)(6), by removing the 

word ‘‘and’’; 

■ d. In paragraph (c)(7), by removing the 

period and adding a semicolon in its 

place; 

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

(9), and (10); 

■ f. By redesignating paragraphs (e) and 

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

respectively; 

■ g. By adding new paragraphs (e) and 

reserved (f); and 

■ h. By revising newly redesignated 

paragraph (g). 

The revisions and additions read as 

follows: 

§ 331.11 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; 


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4Technical assistance and guidance may be 

obtained by contacting APHIS. 

5Nothing in this section is meant to supersede or 

preempt incident response requirements imposed 

by other statutes or regulations. 

6Technical assistance and guidance may be 

obtained by contacting APHIS. 

(ii) Ensure that authorized and 

authenticated users are only granted 

access to select agent and toxin related 

information, files, equipment (e.g., 

servers or mass storage devices), and 

applications as necessary to fulfill their 

roles and responsibilities, and that 

access is modified when the user’s roles 

and responsibilities change or when 

their access to select 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 viruses, worms, spyware) 

from compromising the confidentiality, 

integrity, or availability of information 

systems which manage access to spaces 

registered under this part or records as 

specified in § 331.17; 

(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 § 331.17 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) [Reserved] 

(g) In developing a security plan, an 

individual or entity should consider the 

documents entitled, ‘‘Security Guidance 

for Select Agent or Toxin Facilities.’’ 

This document is available on the 

National Select Agent Registry at 

http://www.selectagents.gov/. 

■ 7. Section 331.12 is amended as 

follows: 

■ a. By revising paragraph (a); 

■ b. By redesignating paragraph (d) as 

paragraph (e); and 

■ c. By adding reserved paragraph (d). 

The revision reads as follows: 

§ 331.12 Biocontainment. 

(a) An individual or entity required to 

register under this part must develop 

and implement a written 

biocontainment plan that is 

commensurate with the risk of the select 

agent or toxin, given its intended use.4

The biocontainment plan must contain 

sufficient information and 

documentation to describe the 

containment procedures for the select 

agent or toxin, including any animals or 

plants intentionally or accidentally 

exposed to or infected with a select 

agent. 

* * * * * 

■ 8. Section 331.13 is amended by 

removing footnote 5 and revising 

paragraph (a) to read as follows: 

§ 331.13 Restricted experiments. 

(a) An individual or entity may not 

conduct, or possess products resulting 

from, the following experiments unless 

approved by and conducted in 

accordance with the conditions 

prescribed by the Administrator: 

(1) Experiments that involve the 

deliberate transfer of, or selection for, a 

drug or chemical 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. 

* * * * * 

■ 9. Section 331.14 is amended as 

follows: 

■ a. In the section heading, by 

redesignating footnote 6 as footnote 5; 

■ b. By revising the first sentence in 

paragraph (a); 

■ c. By redesignating footnote 7 as 

footnote 6; 

■ d. By revising paragraph (b); 

■ e. By redesignating paragraphs (c) and 

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

respectively; and 

■ f. By adding new paragraphs (c) and 

reserved (e). 

The revisions and additions read as 

follows: 

§ 331.14 Incident response.5

(a) An individual or entity required to 

register under this part must develop 

and implement a written incident 

response plan 6 based upon a site 

specific risk assessment. * * * 

(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. 

* * * * * 

■ 10. Section 331.15 is revised to read 

as follows: 

§ 331.15 Training. 

(a) An individual or entity required to 

register under this part must provide 

information and training on 

biocontainment, 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 

(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) [Reserved] 

(c) Refresher training must be 

provided annually for individuals with 

access approval from the HHS Secretary 

or Administrator or at such time as the 


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registered individual or entity 

significantly amends its security, 

incident response, or biocontainment 

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. 

■ 11. Section 331.16 is amended as 

follows: 

■ a. By redesignating footnote 8 as 

footnote 7; 

■ b. By redesignating paragraphs (e) 

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

(f) respectively; 

■ c. By adding a new paragraph (e); 

■ d. In newly redesignated paragraph 

(f), by removing the words ‘‘packaging 

and’’; and 

■ e. By adding a new paragraph (g). 

The additions read as follows: 

§ 331.16 Transfers. 

* * * * * 

(e) 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. 

* * * * * 

(g) 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. 

* * * * * 

■ 12. Section 331.17 is amended as 

follows: 

■ a. By revising paragraph (a)(1) 

introductory text; 

■ b. By redesignating paragraphs (a)(2) 

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

(7), respectively; and 

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

The revision and addition read as 

follows: 

§ 331.17 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); 

* * * * * 

§ 331.19 [Amended] 

■ 13. Section 331.19 is amended as 

follows: 

■ a. By removing paragraph (b)(1)(iv); 

and 

■ b. By redesignating paragraphs 

(b)(1)(v) through (b)(1)(viii) as 

paragraphs (b)(1)(iv) through (b)(1)(vii), 

respectively. 

■ 14. Section 331.20 is revised to read 

as follows: 

§ 331.20 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 Administrator 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 Administrator within 

180 calendar days of the decision. 

(c) The Administrator’s decision 

constitutes final agency action. 

Title 9 

PART 121—POSSESSION, USE, AND 

TRANSFER OF SELECT AGENTS AND 

TOXINS 

■ 15. The authority citation for part 121 

continues to read as follows: 

Authority: 7 U.S.C. 8401; 7 CFR 2.22, 2.80, 

and 371.4. 

■ 16. Section 121.1 is amended as 

follows: 

■ a. In the introductory text of the 

definition of biological agent, by 

removing the word ‘‘rickettsiae,’’; 

■ b. By adding, in alphabetical order, 

definitions of information security, 

occupational exposure, recombinant 

nucleic acids, security barrier, and 

synthetic nucleic acids; and 

■ c. In the introductory text of the 

definition of toxin, by removing the 

word ‘‘rickettsiae,’’. 

The additions read as follows: 

§ 121.1 Definitions. 

* * * * * 

Information security. Protecting 

information and information systems 

from unauthorized access, use, 

disclosure, disruption, modification, or 

destruction in order to provide: 

(1) Integrity, which means guarding 

against improper information 

modification or destruction, and 

includes ensuring information 

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. 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. (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. A physical structure 

that is designed to prevent entry by 

unauthorized persons. 

* * * * * 

Synthetic nucleic acids. (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. 

* * * * * 

■ 17. Section 121.3 is amended as 

follows: 

■ a. By adding a sentence at the end of 

paragraph (a); 

■ b. By revising paragraph (b); 

■ c. In paragraph (c) introductory text, 

by adding the words ‘‘and/or synthetic’’ 

after the word ‘‘recombinant’’ each time 

it appears; 

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

words ‘‘and/or synthetic’’ after the word 

‘‘Recombinant’’; 

■ e. By adding paragraph (d)(3); 

■ f. By revising paragraph (e); and 


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1A virulent Newcastle disease virus (avian 

paramyxovirus serotype 1) has an intracerebral 

pathogenicity index in day-old chicks (Gallus 

gallus) of 0.7 or greater or has an amino acid 

sequence at the fusion (F) protein cleavage site that 

is consistent with virulent strains of Newcastle 

disease virus. A failure to detect a cleavage site that 

is consistent with virulent strains does not confirm 

the absence of a virulent virus. 

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

the words ‘‘Newcastle disease 

virus‘‘(velogenic)’’ and adding the 

words ‘‘virulent Newcastle disease 

virus’’ in their place. 

The revisions and additions read as 

follows: 

§ 121.3 VS 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) VS select agents and toxins: 

African horse sickness virus; African 

swine fever virus; Avian influenza 

virus; Classical swine fever virus; *Footand-mouth disease virus; Goat pox 

virus; Lumpy skin disease virus; 

Mycoplasma capricolum; Mycoplasma 

mycoides; Newcastle disease virus; 1

Peste des petits ruminants virus; 

*Rinderpest virus; Sheep pox virus; 

Swine vesicular disease virus. 

* * * * * 

(d) * * * 

(3) Any low pathogenic strains of 

avian influenza virus, any strain of 

Newcastle disease virus which does not 

meet the criteria for virulent Newcastle 

disease virus, all subspecies 

Mycoplasma capricolum except 

subspecies capripneumoniae 

(contagious caprine pleuropneumonia), 

and all subspecies Mycoplasma 

mycoides except subspecies mycoides 

small colony (Mmm SC) (contagious 

bovine pleuropneumonia), 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 Administrator that 

the attenuated strain or inactivated 

toxin does not pose a severe threat 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. 

* * * * * 

■ 18. Section 121.4 is amended as 

follows: 

■ a. By adding a sentence at the end of 

paragraph (a); 

■ b. By revising paragraph (b); 

■ c. In paragraph (c) introductory text, 

by adding the words ‘‘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 paragraph (d)(3); 

■ f. By revising paragraph (e); and 

■ 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 the 

words ‘‘Burkholderia mallei, and 

Burkholderia pseudomallei’’ in their 

place. 

The revisions and additions read as 

follows: 

§ 121.4 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 

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. 

* * * * * 

§ 121.5 [Amended] 

■ 19. In § 121.5, paragraph (a)(3)(i) is 

amended by removing the words 

‘‘bovine spongiform encephalopathy 

agent,’’. 

■ 20. Section 121.6 is amended as 

follows: 

■ a. In paragraph (a)(3)(i) by removing 

the words ‘‘Brucella melitensis, Hendra 

virus, Nipah virus, Rift Valley fever 

virus, and Venezuelan equine 

encephalitis virus’’ and adding the 

words ‘‘Burkholderia mallei, and 

Burkholderia pseudomallei’’ in their 

place; and 

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

follows: 

§ 121.6 Exemptions for overlap select 

agents and toxins. 

* * * * * 

(e) The Administrator may exempt an 

individual or entity from the 

requirements of this part for 30 calendar 

days if it is necessary to respond to a 

domestic or foreign agricultural 

emergency involving an overlap select 

agent or toxin. The Administrator may 

extend the exemption once for an 

additional 30 days. 

* * * * * 

■ 21. Section 121.9 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); 

■ d. By revising the first sentence of 

paragraph (b); and 

■ e. By revising the first sentence of 

paragraph (c)(1). 

The addition and revisions read as 

follows: 

§ 121.9 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 


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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. 

* * * 

(c) * * * 

(1) The identification of any of the 

following select agents or toxins must be 

immediately reported by telephone, 

facsimile, or email: African horse 

sickness virus, African swine fever 

virus, avian influenza virus (highly 

pathogenic), Bacillus anthracis, 

Burkholderia mallei, Burkholderia 

pseudomallei, classical swine fever 

virus, foot-and-mouth disease virus, 

virulent Newcastle disease virus, 

rinderpest virus, and swine vesicular 

disease virus. * * * 

* * * * * 

■ 22. Section 121.10 is amended as 

follows: 

■ a. By redesignating paragraphs (e) 

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

respectively; 

■ b. By adding a new paragraph (e); and 

■ c. In newly redesignated paragraph (j), 

by removing the number ‘‘5’’ and adding 

the number ‘‘3’’ in its place. 

The addition reads as follows: 

§ 121.10 Restricting access to select 

agents and toxins; security risk 

assessments. 

* * * * * 

(e) A person with valid approval from 

the HHS Secretary or Administrator to 

have access to select agents or 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. 

* * * * * 

■ 23. Section 121.11 is amended as 

follows: 

■ a. By revising paragraph (b); 

■ b. By revising paragraph (c)(2); 

■ c. In paragraph (c)(6), by removing the 

word ‘‘and’’; 

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

(9), and (10); 

■ e. By redesignating paragraphs (e) and 

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

respectively; 

■ f. By adding new paragraphs (e) and 

(f); and 

■ g. By revising newly redesignated 

paragraph (g). 

The revisions and additions read as 

follows: 

§ 121.11 Security. 

* * * * * 

(b) The security plan must be 

designed according to a site-specific risk 

assessment and must provide graded 

protection in accordance with the risk of 

the select agent or toxin, given its 

intended use. A current security plan 

must be submitted for initial 

registration, renewal of registration, or 

when requested. 

(c) * * * 

(2) Contain provisions for the control 

of access to select agents and toxins, 

including the safeguarding of animals or 

plants intentionally or accidentally 

exposed to or infected with a select 

agent, against unauthorized access, 

theft, loss or release. 

* * * * * 

(8) Describe procedures for how the 

responsible official will be informed of 

suspicious activity that may be criminal 

in nature and related to the entity, its 

personnel, or its select agents or toxins; 

and 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 

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 viruses, worms, spyware) 

from compromising the confidentiality, 

integrity, or availability of information 

systems which manage access to spaces 

registered under this part or records as 

specified in § 121.17; 

(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 § 121.17 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 


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9Technical assistance and guidance may be 

obtained by contacting APHIS. 

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 where 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 

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 foot-andmouth disease virus and rinderpest 

virus must have the following 

additional security requirements: 

(i) A minimum of four barriers, one of 

which must be a perimeter security 

fence or equivalent which is monitored 

24 hours a day, 7 days a week (24/7) to 

detect the presence of unauthorized 

persons, vehicles, materials, or 

unauthorized activities; 

(ii) Onsite 24/7 armed security 

response force with roving patrol. 

Response time must not exceed 5 

minutes from the time of an intrusion 

alarm or report of a security incident; 

(iii) CCTV surveillance with 24/7 

monitoring and recording; and 

(iv) Transport vehicle with GPS 

tracking designed to serve as a 

containment vehicle. 

(g) In developing a security plan, an 

individual or entity should consider the 

document entitled, ‘‘Security Guidance 

for Select Agent or Toxin Facilities.’’ 

This document is available on the 

Internet at 

http://www.selectagents.gov/. 

* * * * * 

■ 24. Section 121.12 is amended as 

follows: 

■ a. By revising paragraph (a); 

■ b. By revising paragraph (c)(1); 

■ c. By adding a second sentence to 

paragraph (c)(2); 

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

address ‘‘http://www.aphis.usda.gov/ 

programs/ag_selectagent/index.html ’’ 

and adding in its place ‘‘http:// 

www.selectagents.gov/’’; 

■ e. By redesignating paragraph (d) as 

paragraph (e); and 

■ f. By adding a new paragraph (d). 

The revisions and addition read as 

follows: 

§ 121.12 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.9 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 at http:// 

www.selectagents.gov/. 

(2) * * * This document is available 

on the National Select Agent Registry 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. 

* * * * * 

■ 25. Section 121.13 is amended by 

removing footnote 10 and revising 

paragraphs (a) and (b) to read as follows: 

§ 121.13 Restricted experiments. 

(a) An individual or entity may not 

conduct, or possess products (i.e., select 

agents that are not known to acquire a 

drug resistance trait 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, the 

following experiments unless approved 

by and conducted in accordance with 

the conditions prescribed by the 

Administrator: 

(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. 

* * * * * 

■ 26. Section 121.14 is amended as 

follows: 

■ a. In the section heading, by 

redesignating footnote 11 as footnote 10; 

■ b. In paragraph (a), by redesignating 

footnote 12 as footnote 11 and revising 

the first sentence of paragraph (a); 

■ c. By revising paragraph (b); 

■ d. By redesignating paragraphs (c) and 

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

respectively; and 

■ e. By adding new paragraphs (c) and 

(e). 

The revisions and additions read as 

follows: 


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10Nothing in this section is meant to supersede 

or preempt incident response requirements 

imposed by other statutes or regulations. 

11Technical assistance and guidance may be 

obtained by contacting APHIS. 

§ 121.14 Incident response.10

(a) An individual or entity required to 

register under this part must develop 

and implement a written incident 

response plan 11 based upon a site 

specific risk assessment. * * * 

(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. 

* * * * * 

■ 27. Section 121.15 is revised to read 

as follows: 

§ 121.15 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 

(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. 

■ 28. Section 121.16 is amended as 

follows: 

■ a. By redesignating footnote 14 as 

footnote 12; 

■ b. By redesignating paragraphs (f) 

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

(g), respectively; 

■ c. By adding a new paragraph (f); 

■ d. In newly redesignated paragraph 

(g), by removing the words ‘‘packaging 

and’’; and 

■ e. By adding a new paragraph (h). 

The additions read as follows: 

§ 121.16 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. 

* * * * * 

■ 29. Section 121.17 is amended as 

follows: 

■ a. By revising paragraph (a)(1) 

introductory text; 

■ b. By redesignating paragraphs (a)(2) 

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

(7), respectively; and 

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

The revision and addition read as 

follows: 

§ 121.17 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); 

* * * * * 

■ 30. Section 121.20 is revised to read 

as follows: 

§ 121.20 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 Administrator 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 Administrator within 

180 calendar days of the decision. 

(c) The Administrator’s decision 

constitutes final agency action. 

Done in Washington, DC, this 28th day of 

September 2012. 

Edward Avalos, 

Under Secretary for Marketing and Regulatory 

Programs. 

[FR Doc. 2012–24434 Filed 10–2–12; 11:15 am] 

BILLING CODE 3410–34–P 


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