Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 5823 

specified in 2 CFR 200.334 and the 

requirements of this part; 

* * * * * 

■ 5. Amend § 172.7 by revising 

paragraph (a)(1)(iv)(F), the first sentence 

of paragraph (a)(1)(v)(E), paragraph 

(b)(1)(i), and the first sentence of 

paragraph (b)(5)(i) to read as follows: 

§ 172.7 Procurement methods and 

procedures. 

(a) * * * 

(1) * * * 

(iv) * * * 

(F) The contracting agency shall retain 

supporting documentation of the 

solicitation, proposal, evaluation, and 

selection of the consultant in 

accordance with this section and the 

provisions of 2 CFR 200.334. 

(v) * * * 

(E) The contracting agency shall retain 

documentation of negotiation activities 

and resources used in the analysis of 

costs to establish elements of the 

contract in accordance with the 

provisions of 2 CFR 200.334. * * * 

* * * * * 

(b) * * * 

(1) * * * 

(i) STAs and their subrecipients shall 

comply with procurement requirements 

established in State and local laws, 

regulations, policies, and procedures 

that are not addressed by or are not in 

conflict with applicable Federal laws 

and regulations, as specified in 2 CFR 

part 1201. 

* * * * * 

(5) * * * 

(i) When FAHP funds participate in a 

consultant services contract, the 

contracting agency shall receive 

approval from FHWA, or the STA, as 

appropriate, before utilizing a 

consultant to act in a management 

support role for the contracting agency; 

unless an alternate approval procedure 

has been approved. * * * 

* * * * * 

■ 6. Amend § 172.9 by revising 

paragraph (a)(3)(iv)(B)(1), paragraph 

(c)(1)(iv), and paragraph (d)(1)(vii) to 

read as follows: 

§ 172.9 Contracts and administration. 

(a) * * * 

(3) * * * 

(iv) * * * 

(B) * * * 

(1) Through an additional 

qualifications-based selection 

procedure, which may include, but does 

not require, a formal RFP in accordance 

with § 172.7(a)(1)(ii); or 

* * * * * 

(c) * * * 

(1) * * * 

(iv) Access by the STA, subrecipient, 

FHWA, the U.S. Department of 

Transportation’s Inspector General, the 

Comptroller General of the United 

States, or any of their duly authorized 

representatives to any books, 

documents, papers, and records of the 

consultant which are directly pertinent 

to that specific contract for the purpose 

of making audit, examination, excerpts, 

and transcriptions; 

* * * * * 

(d) * * * 

(1) * * * 

(vii) Documenting contract 

monitoring activities and maintaining 

supporting contract records, as specified 

in 2 CFR 200.334. 

* * * * * 

■ 7. Amend § 172.11 by revising 

paragraph (b)(1)(iii) introductory text, 

the second and third sentences of 

paragraph (c)(2) introductory text, the 

second sentence of paragraph (c)(3)(i), 

and the second and third sentences of 

paragraph (d) to read as follows: 

§ 172.11 Allowable costs and oversight. 

* * * * * 

(b) * * * 

(1) * * * 

(iii) When the indirect cost rate has 

not been established by a cognizant 

agency in accordance with paragraph 

(b)(1)(ii) of this section, the STA shall 

perform an evaluation of a consultant’s 

or subconsultant’s indirect cost rate 

prior to acceptance and application of 

the rate to contracts administered by the 

STA or its subrecipients. The evaluation 

performed by STAs to establish or 

accept an indirect cost rate shall provide 

assurance of compliance with the 

Federal cost principles and may consist 

of one or more of the following: 

* * * * * 

(c) * * * 

(2) * * * An STA may employ a riskbased oversight process to provide 

reasonable assurance of consultant 

compliance with Federal cost principles 

on FAHP funded contracts administered 

by the STA or its subrecipients. If 

employed, this risk-based oversight 

process shall be incorporated into STA 

written policies and procedures, as 

specified in § 172.5(c). * * * 

* * * * * 

(3) * * * 

(i) * * * The certification 

requirement shall apply to all indirect 

cost rate proposals submitted by 

consultants and subconsultants for 

acceptance by an STA. * * * 

* * * * * 

(d) * * * FHWA, STAs, and 

subrecipients of FAHP funds may share 

audit information in complying with the 

STA’s or subrecipient’s acceptance of a 

consultant’s indirect cost rates pursuant 

to 23 U.S.C. 112 and this part provided 

that the consultant is given notice of 

each use and transfer. Audit information 

shall not be provided to other 

consultants or any other government 

agency not sharing the cost data, or to 

any firm or government agency for 

purposes other than complying with the 

STA’s or subrecipient’s acceptance of a 

consultant’s indirect cost rates pursuant 

to 23 U.S.C. 112 and this part without 

the written permission of the affected 

consultants. * * * 

[FR Doc. 2024–01705 Filed 1–29–24; 8:45 am] 

BILLING CODE 4910–22–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

[Docket No. CDC–2020–0024] 

42 CFR Part 73 

RIN 0920–AA71 

Possession, Use, and Transfer of 

Select Agents and Toxins; Biennial 

Review of the List of Select Agents and 

Toxins 

AGENCY: Centers for Disease Control and 

Prevention (CDC), Department of Health 

and Human Services (HHS). 

ACTION: Notice of proposed rulemaking. 

SUMMARY: In accordance with the Public 

Health Service Act, the Department of 

Health and Human Services (HHS) 

Centers for Disease Control and 

Prevention (CDC) reviewed the HHS list 

of select agents and toxins with the 

potential to pose a severe threat to 

public health and safety. HHS/CDC 

proposes to amend the list by removing 

three biological agents, raising one 

toxin’s exclusion amounts, renaming a 

virus, designating a current agent as a 

Tier 1 agent, and removing the 

designation of Tier 1 status from one 

agent. HHS/CDC also proposes to clarify 

language and add requirements as 

discussed below. 

DATES: Submit written or electronic 

comments by April 1, 2024. 

ADDRESSES: You may submit comments, 

identified by Docket No. CDC–2020– 

0024 or Regulation Identifier Number 

(RIN) 0920–AA71, by any of the 

following methods: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

• Mail: Division of Regulatory 

Science and Compliance, Centers for 

Disease Control and Prevention, 1600 

Clifton Road NE, Mailstop H21–4, 


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Atlanta, Georgia 30329, ATTN: RIN 

0920–AA71. 

Instructions: All submissions received 

must include the agency name and RIN 

for this rulemaking. All relevant 

comments received will be posted 

without change to http://

www.regulations.gov, including any 

personal information provided. Do not 

send comments by email; CDC does not 

accept public comment by email. 

Docket Access: For access to the 

docket to read background documents 

or comments received, or to download 

an electronic version of the notice of 

proposed rulemaking, go to http://

www.regulations.gov. 

FOR FURTHER INFORMATION CONTACT: 

Samuel S. Edwin Ph.D., Director, 

Division of Regulatory Science and 

Compliance, Centers for Disease Control 

and Prevention, 1600 Clifton Road NE, 

Mailstop H21–7, Atlanta, Georgia 30329. 

Telephone: (404) 718–2000. 

SUPPLEMENTARY INFORMATION: The 

Notice of Proposed Rulemaking (NPRM) 

is organized as follows: 

I. Public Participation 

II. Background 

A. Legal Authority 

B. 2020 ANPRM 

III. Summary of Proposed Changes to 42 CFR 

Part 73 

A. Definitions 

B. Removal of Brucella abortus, Brucella 

melitensis, and Brucella suis 

C. Botulinum Neurotoxin Producing 

Species of Clostridium 

D. Hantaviruses 

E. Toxin Review: Changes to Exclusion 

Limits for Short, Paralytic Alpha 

Conotoxins 

F. Renaming Ebola Virus to the Genus 

Ebolavirus 

G. Designating Nipah Virus as a Tier 1 

Select Agent 

H. Adding a Footnote to the HHS Select 

Agent List 

I. Discovery of Select Agents or Toxins 

J. Non-Possession of Select Agents or 

Toxins by a Registered Entity 

K. Electronic Federal Select Agent Program 

(eFSAP) Information System 

L. Registration 

M. Tier 1 Security Enhancements 

N. Biosafety—Facility Verification 

O. Biosafety—Effluent Decontamination 

System 

P. Restricted Experiments 

Q. Training 

R. Records 

S. Codifying Existing Policies 

IV. Alternatives Considered 

V. Required Regulatory Analyses 

A. Executive Orders 12866,13563, and 

14094 

B. The Regulatory Flexibility Act 

C. Paperwork Reduction Act of 1995 

D. E.O. 12988: Civil Justice Reform 

E. E.O. 13132: Federalism 

F. Plain Language Act of 2010 

VI. References 

I. Public Participation 

Interested persons or organizations 

are invited to participate by submitting 

written views, recommendations, and 

data. Comments are welcomed on any 

topic related to this notice. 

In addition, HHS/CDC invites 

comments specifically as to whether 

there are additional biological agents or 

toxins that should be added or removed 

from the HHS list of select agents and 

toxins based on the following criteria 

outlined under 42 U.S.C. 262a(a)(1)(B): 

(1) ‘‘The effect on human health of 

exposure to the agent or toxin’’ 

(2) ‘‘The degree of contagiousness of 

the agent or toxin and the methods by 

which the agent or toxin is transferred 

to humans’’ 

(3) ‘‘The availability and effectiveness 

of pharmacotherapies to treat or 

immunizations to prevent any illness 

resulting from infection by the agent or 

exposure to the toxin’’ 

(4) ‘‘Any other criteria including the 

needs of children and other vulnerable 

populations’’ and any other criteria that 

the commenter believes should be 

considered. 

Comments received, including 

attachments and other supporting 

materials, are part of the public record 

and subject to public disclosure. 

Commenters should not include any 

information in their comments or 

supporting materials that they consider 

confidential or inappropriate for public 

disclosure. HHS/CDC will carefully 

consider all comments submitted in 

preparation of a final rule. Do not send 

comments by email. CDC does not 

accept public comment by email. 

II. Background 

A. Legal Authority 

Under the Public Health Security and 

Bioterrorism Preparedness and 

Response Act of 2002 (Bioterrorism 

Response Act), the HHS Secretary must 

establish by regulation, a list of 

biological agents and toxins that have 

the potential to pose a severe threat to 

public health and safety (42 U.S.C. 

262a(a)(1)). In determining whether to 

include a biological agent or toxin on 

the list, the Bioterrorism Response Act 

requires that the HHS Secretary 

consider the following criteria: the effect 

on human health of exposure to an 

agent or toxin; the degree of 

contagiousness of the agent and the 

methods by which the agent or toxin is 

transferred to humans; the availability 

and effectiveness of pharmacotherapies 

and immunizations to treat and prevent 

illnesses resulting from an agent or 

toxin; and any other criteria, including 

the needs of children and other 

vulnerable populations that the HHS 

Secretary deems relevant (42 U.S.C. 

262a(a)(1)(B)). 

Under 42 U.S.C. 262a(a)(2), the HHS 

Secretary must review and republish the 

list of HHS select agents and toxins at 

least biennially. For this review, HHS/ 

CDC evaluated as discussed below each 

agent and toxin based on: the degree of 

pathogenicity (ability of an organism to 

cause disease); dissemination efficacy; 

aerosol stability; matrix stability; ease of 

production; ability to genetically 

manipulate or alter; severity of illness; 

case fatality rate; long-term health 

effects; rate of transmission; available 

treatment; status of host immunity (e.g. 

whether an individual has already been 

exposed to the agent and generated an 

immune response); vulnerability of 

special populations; decontamination 

and restoration (the extent remediation 

efforts are needed due to agent 

persistence in the environment and 

population); and the burden or impact 

on the health care system. 

As noted above, the list of HHS select 

agents and toxins is divided into two 

sections. The biological agents and 

toxins listed in 42 CFR 73.3 (HHS select 

agents and toxins) have the potential to 

pose a severe threat to human health 

and safety and are regulated only by 

HHS. The biological agents listed in 

73.4 (overlap select agents and toxins) 

have not only the potential to pose a 

severe threat to human health and 

safety, but have also been determined by 

the USDA, pursuant to USDA’s 

authority under the Agriculture 

Bioterrorism Protection Act of 2002 (7 

U.S.C. 8401), to have the potential to 

pose a severe threat to animals and 

animal products. Accordingly, these 

biological agents are jointly regulated by 

HHS and USDA as ‘‘overlap’’ select 

agents. The Bioterrorism Response Act 

defines the term ‘‘overlap agents and 

toxins’’ to mean biological agents and 

toxins that are listed pursuant to 42 

U.S.C. 262a(a)(1) and listed pursuant to 

7 U.S.C. 8401(a)(1). See 42 U.S.C. 

262a(l) and 7 U.S.C. 8401(l). If HHS/ 

CDC removes any overlap select agents 

from its list, these agents might still be 

regulated as USDA select agents 

dependent on the outcome of the USDA 

biennial review. The Federal Select 

Agent Program (FSAP) is the 

collaboration of the CDC, Division of 

Regulatory Science and Compliance 

(previously known as the Division of 

Select Agents and Toxins) and the 

USDA Animal and Plant Health 

Inspection Service (APHIS), Division of 

Agricultural Select Agents and Toxins 

to administer the select agent 

regulations and coordinate federal 

oversight of select agents and toxins in 


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a manner to minimize the 

administrative burden on the regulated 

community. 

B. 2020 ANPRM 

On March 17, 2020, we published an 

advance notice of proposed rulemaking 

(ANPRM) (85 FR 15087) in which we 

stated that we were requesting 

comments on whether to retain or 

remove three species of Brucella (B. 

abortus, B. melitensis, and B. suis), 

Rickettsia prowazekii, Coxiella burnetii, 

Bacillus anthracis (Pasteur strain), 

Botulinum neurotoxin producing 

species of Clostridium, and Venezuelan 

Equine Encephalitis Virus (VEEV) 1AB 

and 1C. We received 335 comments 

from the ANPRM. Regarding the request 

for comment on whether to retain or 

remove R. prowazekii, C. burnetii, B. 

anthracis (Pasteur strain), Botulinum 

neurotoxin producing species of 

Clostridium, and VEEV from the select 

agent and toxins list, HHS/CDC received 

27 comments from individuals, animal 

health groups, regulated communities 

and public health associations that had 

mixed opinions on removing and 

retaining the agents. Of the 16 

commenters who supported delisting, 

the majority of comments supported the 

delisting of C. burnetii and C. 

botulinum. Six commenters believed 

that C. burnetii should be delisted to 

allow for effective research can be 

conducted towards the development of 

improved vaccination for livestock, 

diagnostics, and other livestock 

management options and one 

commenter argued many people may 

have already been exposed, 

approximately 60% of exposures remain 

asymptomatic, and a significant portion 

of the population may already have 

immunity. Besides the five comments 

that cited information found in the 

ANPRM as a basis for removal, one 

commenter added that the disease 

botulism is caused by intoxication with 

protein toxins, botulinum neurotoxins, 

and not by intoxication with C. 

botulinum. Another commenter 

indicated that spores of botulinum 

neurotoxin species of Clostridium, used 

to conduct food challenge studies 

should be excluded from the 

requirements of the regulations. There 

was only one comment each in support 

of delisting R. prowazekii, VEEV, and B. 

anthracis (Pasteur strain) that supported 

information found in ANPRM. After 

carefully reviewing the public 

comments and considerations for 

determining whether to include an 

agent or toxin on the list as articulated 

in 42 U.S.C. 262a, we are proposing to 

retain Rickettsia prowazeckii, Coxiella 

burnetii, VEEV, and B. anthracis 

(Pasteur strain) from the select agents 

and toxins list. The additional changes 

we are moving forward with in this 

proposed rule can be found listed below 

including proposing the removal of 

Brucella abortus, Brucella melitensis, 

and Brucella suis. We also are proposing 

to raise exclusion amounts for 

conotoxin, renaming Ebola virus, 

designating Nipah virus as a Tier 1 

select agent, and removing the 

designation of Tier 1 status from 

Botulinum neurotoxin producing 

species of Clostridium. We appreciate 

all comments received from the ANPRM 

and will consider these comments in 

future deliberations. 

III. Summary of Proposed Changes to 

42 CFR Part 73 

The following changes to the list of 

HHS select agents and toxins are 

proposed based on comments received 

in response to the advance notice of 

proposed rulemaking (85 FR 15087) and 

final rule (82 FR 6278). 

HHS/CDC newly proposes to add 

definitions and provisions to further 

clarify inactivation of select agents; 

adding requirements for reporting 

discoveries of select agents and toxins; 

provisions regarding effluent 

decontamination system; and biosafety 

provisions for facility verification 

requirements for registered biosafety 

level 3 and animal biosafety level 3 

laboratories. 

HHS/CDC also newly proposes to 

remove Brucella abortus, Brucella 

melitensis, and Brucella suis from the 

select agent list; update the terminology 

and clarify the specific clade that is a 

select agent by changing ‘‘Monkeypox 

virus’’ to ‘‘Mpox virus (clade I)’’; and to 

change ‘‘SARS coronavirus (SARS– 

CoV)’’ to ‘‘Severe acute respiratory 

syndrome coronavirus (SARS–CoV)’’ to 

correct the nomenclature; and to remove 

the exclusion regarding South American 

genotype of Eastern Equine Encephalitis 

virus as this terminology is no longer 

the correct nomenclature. HHS/CDC is 

interested in comments regarding these 

proposed revisions. 

In addition, HHS/CDC is proposing to 

incorporate existing policies previously 

published and found at www.select

agents.gov into regulations and is 

soliciting public comments on these 

policies, further discussed below, 

regarding roles of the Responsible 

Official and Alternate Responsible 

Official, chemical inactivation of 

tissues, conclusion of patient care, 

annual internal inspections, inactivation 

certificates, deviation from a validated 

inactivation procedure or a viable select 

agent removal method, studies 

involving naturally infected animals, 

formalin-fixed paraffin-embedded 

tissues containing a select agent, 

validated inactivation procedures, and 

in-house validation. This is a standard 

practice for HHS/CDC to utilize policy 

to first refine its practices before 

codification. This helps to ensure that 

regulated entities are able to implement 

the requirements. In addition, HHS/CDC 

proposes to correct editorial errors. By 

codifying these existing policies into 

regulation, HHS/CDC aims to provide 

clarity and stability in program 

requirements, make compliance more 

straightforward for regulated entities, 

and ensure enforcement is consistent 

and predictable across the regulated 

community. 

Specifically, HHS/CDC is seeking 

comments on whether any of the 

proposed changes would create an 

additional burden in implementing the 

proposed changes. 

A. Definitions 

HHS/CDC is proposing to add or 

revise the following eight terms to 

section 73.1 of the regulations 

(Definitions) to clarify the use of these 

terms in the regulations. 

The ‘‘loss,’’ ‘‘release,’’ and ‘‘theft’’ 

definitions are proposed to be added to 

assist the regulated community on what 

is to be reported as required under 

Section 19. The definition of 

‘‘discovery’’ relates to the proposed new 

reporting requirement further discussed 

below. The addition of proposed 

definitions of ‘‘validated removal 

procedure’’ and ‘‘verification viability 

testing protocol’’ and the revisions of 

‘‘validated inactivation procedure’’ and 

‘‘viability testing protocol’’ will provide 

clarity on inactivation provisions 

outlined in regulations in Sections 3, 4, 

9 and 17. The new terms include: 

• Discovery means the finding of a 

select agent or toxin by an individual or 

entity that is not aware of the select 

agent or toxin’s existence. Examples 

include, but are not limited to, the 

following: 

(1) A registered individual or entity 

finds a select agent or toxin not 

accounted for in their inventory; or 

(2) A non-registered individual or 

entity finds a select agent or toxin. 

• Loss means the inability to account 

for a select agent or toxin known to be 

in the individual’s or entity’s 

possession. 

• Release means any of the following: 

(1) an incident resulting in 

occupational exposure to a select agent 

or toxin, 

(2) an incident resulting in animal/ 

plant exposure to a select agent or toxin, 

(3) the failure of equipment used to 

contain a select agent or toxin such that 


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it is reasonably anticipated that a select 

agent or toxin was released, 

(4) the failure of or breach in personal 

protective equipment in the presence of 

a select agents or toxin, or 

(5) the failure of biosafety procedures 

such that it is reasonably anticipated 

that a select agent or toxin was outside 

of containment. 

• Theft means the unauthorized 

taking and removing of a select agent or 

toxin from the possession of an 

individual or entity. 

• Validated removal procedure means 

a procedure, whose efficacy has been 

confirmed by data generated in-house 

from a viability testing protocol, to 

remove all viable select agent, or nucleic 

acids of any select agent virus capable 

of producing infectious virus. 

• Verification viability testing 

protocol means a protocol, used on 

samples that have been subjected to a 

validated inactivation or removal 

procedure, to confirm the material is 

free of all viable select agent, or nucleic 

acids of any select agent virus capable 

of producing infectious virus. 

Existing definitions being revised 

include: 

• Validated inactivation procedure 

means a procedure, whose efficacy has 

been confirmed by data generated from 

an in-house viability testing protocol, to 

render a select agent non-viable but 

allows the select agent to retain 

characteristics of interest for future use; 

or to render any nucleic acids that can 

produce infectious forms of any select 

agent virus non-infectious for future 

use. 

• Viability testing protocol means a 

protocol used to confirm the efficacy of 

the inactivation or removal procedure 

by demonstrating the material is free of 

all viable select agent, or nucleic acids 

of any select agent virus capable of 

producing infectious virus. 

B. Removal of Brucella abortus, Brucella 

melitensis, and Brucella suis 

HHS/CDC is proposing removing B. 

abortus, B. melitensis, and B. suis from 

the select agents and toxins list based on 

a review of considerations outlined 

under 42 U.S.C. 262a(a)(1)(B). That 

provision calls for consideration of (1) 

an agent’s effect on human health, (2) 

degree of contagiousness, (3) the 

availability and effectiveness of 

pharmacotherapies and immunizations, 

and (4) other appropriate criteria as 

determined by the HHS Secretary. With 

regard to the effect on human health, 

Brucella infections have a low case 

fatality rate, with an untreated fatality 

rate usually ranging from 1–2% of those 

identified with the infection (Spickler, 

2018). Brucellosis typically causes mild 

clinical symptoms (flu-like illness) 

(Olsen et al., 2018). With regard to the 

degree of contagiousness, there is no 

indication that Brucella is transmitted 

between people by casual contact under 

ordinary conditions. Humans are 

typically infected from exposure to 

animal reservoirs or animal products; 

transmission to humans from wildlife is 

a rare event unless an individual 

directly handles infected animals, such 

as in butchering meat (Godfroid et al., 

2013). With regard to the availability of 

effective pharmacotherapies, disease 

caused by these bacteria is treatable 

with antibiotics (Spickler, 2018). 

In the ANPRM, HHS/CDC sought 

comments on whether B. abortus, B. 

melitensis, and B. suis should be 

removed or retained on the select agents 

and toxins list, with a substantial 

majority supporting removal of the 

agents. HHS/CDC received four 

comments recommending the retention 

of B. abortus, B. melitensis, and B. suis 

on the list of select agents and toxins. 

One commenter indicated that if state 

public health laboratories no longer 

accept specimens suspected as 

containing these Brucella species for 

confirmatory testing, then the burden of 

such confirmatory testing will fall upon 

the sentinel laboratories of the 

Laboratory Response Network (LRN). 

The commenter further argued that all 

clinical laboratories do not have the 

engineering controls (e.g., biological 

safety cabinets) needed to perform these 

procedures safely and there could be a 

risk of occupational health and safety 

concerns if identification activities are 

not done with appropriate care. 

Regardless of an agent’s status on the 

select agent list, clinical laboratories 

will likely continue to be exposed to 

these agents when conducting 

diagnostic procedures or working with 

unknown samples if sufficient biosafety 

and personal protective measures are 

not taken. Furthermore, removing an 

agent from the select agents and toxins 

list does not preclude state laboratories 

from providing testing; HHS/CDC does 

not direct the testing provided by these 

laboratories. The other commenter 

agreed with retention because 

Brucellosis is a very serious human 

disease and Brucella spp. are easily 

spread in a laboratory environment 

where laboratory acquired cases are not 

rare. Another commenter stated that 

Brucella species are known to have a 

low infectious dose and therefore 

present an increased risk of infection 

due to laboratory exposures. In addition, 

Brucella is the top laboratory acquired 

infection reported by clinical 

laboratories to public health 

laboratories. If removed from the select 

agent list, the commenter stated that it 

is likely that hospitals will no longer 

report these exposures, leaving many 

laboratorians at risk. For these reasons, 

the commenter recommended that 

Brucella should be stringently regulated 

and therefore remain as a select agent. 

While HHS/CDC agrees with the 

commenters that Brucella has a low 

infectious dose, the case fatality rate and 

person-to-person transmission for 

Brucella continues to be very low. In 

addition, the human illnesses are 

readily recognized and treated. 

HHS/CDC received 36 comments that 

supported removal based on the 

considerations provided in the ANPRM 

and stated that the agents should be 

removed so that important research can 

be conducted to include vaccine 

development. Another 286 commenters 

supported the removal of B. abortus to 

reduce the regulatory burden so that 

effective research can be conducted 

towards the development of improved 

vaccination for livestock, diagnostics, 

and other livestock management 

options. Two commenters supported the 

removal of B. abortus and B. suis to 

reduce the regulatory burden to further 

the development of diagnostic testing, 

effective vaccines, and further 

assistance in controlling the agent. 

Another commenter believes B. abortus 

and B. suis to be poor selections for a 

biological agent. While B. suis was one 

of the first bioweapons developed by the 

United States in the 1950s, there have 

been many more insidious and potent 

pathogens that have been identified in 

the past 70 years (Olsen et al., 2018). 

Although B. abortus and B. suis have 

zoonotic capabilities, humans are 

essentially dead-end hosts for 

brucellosis making it improbable that an 

infected person can transmit the disease 

to another person (Olsen et al., 2018). 

Other disease characteristics of 

brucellosis, including mild clinical 

symptoms, the long incubation period, 

positive response to antibiotic/ 

pharmacotherapy treatment, low risk of 

human-to-human transmission, and low 

mortality rate, further decrease the 

attractiveness of B. abortus, B. 

melitensis, and B. suis as bioweapons 

(Centers for Disease Control and 

Prevention, 2017; Cross et al., 2019; 

Shakir, 2021). 

In accordance with the criteria and 

considerations for determining whether 

to include an agent or toxin on the list 

as articulated in 42 U.S.C. 262a, HHS/ 

CDC is proposing to remove B. abortus, 

B. melitensis, and B. suis from the HHS 

select agents and toxins list. The 

minimal effects on human health upon 

exposure to these agents, the degree of 


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contagiousness of these agents, the 

methods by which these agents are 

transferred to humans, and the 

availability and effectiveness of 

pharmacotherapies to treat illness 

resulting from these agents are key 

considerations for this proposal. HHS/ 

CDC would be interested in comments 

on this proposal. Please provide a 

detailed explanation for your response. 

Since B. abortus, B. melitensis, and B. 

suis are overlap select agents, even if 

HHS/CDC removes them from its list, 

these agents might still be regulated as 

USDA select agents dependent on the 

outcome of USDA biennial review. 

C. Botulinum Neurotoxin Producing 

Species of Clostridium 

Botulism is a serious paralytic disease 

caused by a neurotoxin produced during 

the growth of the spore-forming 

bacterium Clostridium botulinum (or 

rarely, C. argentinense (Puig de Centorbi 

et al., 1997), C. butyricum, or C. baratii) 

(Sobel, 2005). In the ANPRM, HHS/CDC 

requested comment on whether this 

agent should be removed or retained 

from the select agents and toxins list 

because the organism does not normally 

cause disease. At this time, HHS/CDC is 

proposing to retain Botulinum 

neurotoxin producing species of 

Clostridium as an HHS select agent 

because it produces the highly toxic 

Botulinum neurotoxin (a select toxin). 

Given the risk that the agent can 

produce such a potent toxin, HHS/CDC 

is proposing to retain this organism as 

an HHS select agent; however, HHS/ 

CDC is also proposing that because the 

organism itself does not normally cause 

disease, it no longer be listed as a Tier 

1 agent. 

HHS/CDC received mixed reactions 

on whether to retain or remove the 

agent. Six comments supported the 

retention of the agent; however, five 

supported the removal. Besides the 

information included in the ANPRM for 

removal, that the organism does not 

cause disease, one commenter added 

that the disease botulism is caused by 

intoxication with protein toxins, 

botulinum neurotoxins, and not by 

intoxication with C. botulinum. 

Therefore, the commenter further 

explained that human botulism cases 

are rare and can be managed with 

antitoxin treatments. 

HHS/CDC received one comment that 

spores of botulinum neurotoxin species 

of Clostridium, used to conduct 

experimental food challenge studies, 

should be excluded from the HHS list of 

select agents because: 

• Basic biological safety practices are 

already sufficient to protect laboratory 

personnel and the public. 

• Inoculated food samples replicate 

the concentrations of spores that may be 

naturally found in the foods or soils or 

sediments. 

• Botulinum spores are not infectious 

to the general public of healthy 

individuals older than 1 year of age. 

• Toxin production for inoculated 

samples is no greater than that which 

may occur naturally if a consumer were 

to mishandle or temperature-abuse low 

acid foods. 

HHS/CDC disagreed that experimental 

food challenge studies should be 

excluded from the regulations. Since 

this work would require possession and 

manipulation of the select agent 

Botulinum neurotoxin producing 

species of Clostridium, and is not 

diagnostic in nature, this work is not 

exempted from the select agent and 

toxin regulations. Cells or spores of 

botulinum neurotoxin producing 

species of Clostridia are introduced into 

the samples intentionally. Therefore, 

this work would be regulated by the 

select agent regulations. 

Six commenters did not support the 

removal of botulinum neurotoxin 

producing species of Clostridia. One 

commenter recommended that the 

organism not be considered as Tier 1 

select agent. Two commenters argued 

the bacteria grows and produces toxin 

relatively easily (Peck, 2009). One 

commenter further claimed that 

normally the bacterium exists in the 

environment as a dormant spore; 

however, in environments such as in 

canned foods, deep wounds, or the 

intestinal tract, the spores germinate 

into vegetative bacteria. Two 

commenters stated that with access to 

these strains, a simplistic grocery-grade 

broth filled to the maximum volume or 

neck of a container is enough for the 

criminals to drive the fermentation 

process following inoculation of such 

strains. Another commenter argued that 

a botulism outbreak, whether natural or 

deliberate, can quickly overwhelm local 

health care systems. Commenters 

further disagreed with the comparison 

of the organism to S. aureus not being 

regulated, but that its toxins are because 

the commenters stated that 

Staphylococcal enterotoxins are not 

nearly as potent and fatal as botulinum 

neurotoxin. The other commenter 

disagreed because in order to produce 

the purified botulinum neurotoxins that 

are used in medicine, food safety, and 

other fields, the commenter argued that 

it is essential to secure strains or 

recombinant organisms of 

neurotoxigenic Clostridia for consistent 

production of high-quality botulinum 

neurotoxins (i.e., those strains that 

produce true toxins). Another 

commenter argued that a terrorist could 

use the crude toxin cell extracts and not 

purified toxin for weaponization 

purposes. Two commenters stated that 

the removal of the agent status could set 

a wrong precedence for recombinant 

strains to express biologically active 

toxin for easy and bulk production. A 

commenter also indicated that medical 

clinicians often use highly purified 

toxins, but these still need to be made 

by neurotoxigenic organisms including 

special strains. As the toxin produced 

by these species remains regulated, a 

commenter stated that the agent should 

be retained since it is not currently 

standard practice for public health 

laboratories to quantify toxin levels 

following identification of C. botulinum. 

If the agent is retained as an HHS select 

agent, two commenters requested that 

changes be made to the regulations to: 

(i) relax the current inventory format of 

maintaining stocks or working stocks; 

(ii) relax or remove in-house validation 

and verification requirements (to test 

10% volume or sample size subjected to 

agent inactivation and/or removal 

procedures), while implementation of a 

terminal filtration step to remove the 

cells or spore forms from the research or 

analytical samples needs to be 

continued to ensure the security of the 

agent; and (iii) include more waiver 

provisions for bona fide research as 

needed, or on a case by case basis (e.g., 

food challenge studies, countermeasure 

development, emergencies, proficiency 

testing and diagnostics etc.). HHS/CDC 

disagreed with the commenters that 

certain provisions should be relaxed. If 

an individual or entity is registered to 

possess, use, or transfer a select agent, 

then the individual or entity is required 

to meet all the regulatory requirements 

for the select agent. It should be noted 

that the current regulations do not 

contain provisions regarding ‘‘working 

stocks’’ and contain a provision for an 

individual or entity to obtain a waiver 

for ‘‘a select agent or regulated nucleic 

acids that can produce infectious forms 

of any select agent virus not subjected 

to a validated inactivation procedure or 

material containing a select agent not 

subjected to a procedure that removes 

all viable select agent cells, spores, or 

virus particles if the material is 

determined by the HHS Secretary to be 

effectively inactivated or effectively free 

of select agent’’ (See 73.3 (d)(6)). 

In accordance with the criteria and 

considerations for determining whether 

to include an agent or toxin on the list 

articulated in 42 U.S.C. 262a, HHS/CDC 

agreed with the six commenters to 

retain botulinum neurotoxin producing 

species of Clostridia as an HHS select 


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agent. HHS/CDC made the 

determination because the toxin is 

easily secreted by botulinum neurotoxin 

producing species of Clostridia which 

makes it simple to isolate the lethal 

toxin. 

HHS/CDC also agreed and has 

determined that the botulinum 

neurotoxin producing species of 

Clostridia should no longer be identified 

as a Tier 1 select agent. Tier 1 select 

agents and toxins pose a severe threat to 

public health and safety and are 

considered to present the greatest risk of 

deliberate misuse with significant 

potential for mass casualties or 

devastating effect to the economy, 

critical infrastructure, or public 

confidence. Because the organism itself 

does not meet this definition and does 

not normally cause widespread disease, 

HHS/CDC does not believe the organism 

should be designated as a Tier 1 select 

agent. HHS/CDC would continue to 

retain Botulinum neurotoxins as a Tier 

1 agent. HHS/CDC would be interested 

in comments on retaining botulinum 

neurotoxin producing species of 

Clostridia as an HHS select agent and 

not as a Tier 1 select agent. Please 

provide a detailed explanation for your 

response. 

D. Hantaviruses 

In the 2020 ANPRM, HHS/CDC 

requested public comment on whether 

Sin Nombre virus (SNV), Andes virus 

(ANDV), Hantaan virus (HTNV), and 

Dobrava virus (DOBV) should be 

considered HHS select agents given the 

fatality rate and low infectious/lethal 

doses of these viruses. Based on a 

review of considerations outlined under 

42 U.S.C. 262a(a)(1)(B) and the public 

comments submitted by subject matter 

experts, HHS/CDC is not proposing to 

add these viruses to the select agent list. 

Specifically, the very limited direct 

person-to-person transmission of 

hantaviruses, the difficulty of 

propagating the organisms in a 

laboratory setting, and the fact that the 

infectious dose of hantavirus for 

humans is higher than the doses 

provided in ANPRM indicate that these 

viruses are not appropriate for inclusion 

on the select agent list. 

HHS/CDC received one comment that 

supported this addition of the viruses as 

HHS select agents. HHS/CDC received 

three comments that did not support the 

addition of these viruses as HHS select 

agents. The commenters who did not 

support listing argued that adding these 

viruses will result in a significant 

burden on research institutions. For 

those institutions that already have a 

select agent program and registered 

laboratories established, one commenter 

argued adding new agents may crowd 

existing laboratory spaces and will 

likely result in slowed research and 

development of vaccines and treatments 

for all agents studied within the space. 

The commenter further explained that 

new requirements would take 

considerable time, delay critical 

research programs, and require 

increased funding. Two commenters 

presented the following reasons to not 

include these viruses as select agents: 

• Current laboratory practices and 

biosafety regulations do not expose 

research personnel and the larger 

community to high risk of hantavirus 

infection (e.g., direct person-to-person 

transmission of hantaviruses has not 

been documented for any hantavirus, 

except for very limited confirmed events 

for Andes virus in South America; 

laboratory-acquired infections have not 

been documented for these viruses since 

the adoption of ABSL–3 (HTNV, DOBV) 

and ABSL–4 (SNV, ANDV) practices; 

and lack of approved therapeutics and 

vaccines is not sufficient criteria for 

select agent inclusion based on other 

emerging RNA virus classifications 

(such as West Nile virus, Zika virus, 

Powassan virus, many non-endemic 

Influenza A viruses, chikungunya 

virus). 

• The infectious dose of any 

hantavirus for humans is likely much 

higher than those presented in the 

proposal, as evidenced by non-human 

primate studies and strikingly rare 

infections despite endemicity in rodent 

reservoirs and significant ecological 

overlap between humans and reservoirs. 

• These viruses do not pose a 

national security threat as potential 

bioweapons due to the notoriously 

challenging culture conditions of even 

laboratory-adapted strains and the 

scarcity of tractable animal models or 

amplifying hosts. 

• This designation of select agent 

status will significantly disrupt ongoing 

research operations. 

HHS/CDC agreed with two 

commenters and has decided not to 

propose adding these Hantaviruses as 

HHS select agents. As explained above, 

there has been very limited direct 

person-to-person transmission. In 

addition, the infectious dose for humans 

is likely higher than the doses provided 

in ANPRM, and it is difficult to 

propagate in a laboratory setting. HHS/ 

CDC would be interested in comments 

on adding these Hantaviruses as HHS 

select agents. Please provide a detailed 

explanation for your response. 

E. Toxin Review: Changes to Exclusion 

Limits for Short, Paralytic Alpha 

Conotoxins 

HHS/CDC is proposing to increase the 

exclusion amount for short, paralytic 

alpha conotoxins from 100mg to 200mg 

based on assessments of lethal doses of 

conotoxin compared to other regulated 

toxins and the amount of the toxin that 

would be needed if a bad actor sought 

to weaponize it. 

In the 2020 ANPRM (85 FR 15087), 

HHS/CDC requested comments on 

whether any toxins should be retained, 

removed, or if the exclusion amount for 

each toxin should be increased or 

decreased. Specifically, HHS/CDC 

requested comments for short, paralytic 

alpha conotoxins containing the 

following amino acid sequence 

X1CCX2PACGX3X4X5X6CX7. Alpha 

conotoxins are low, molecular weight 

toxins that are isolated from the venom 

bulb of the marine cone snail. These 

toxins present a public health threat 

because they are highly toxic, more 

stable, and can persist for longer periods 

of time in the environment. Additional 

toxins requested for public comment 

include Diacetoxyscirpenol and 

Staphylococcal enterotoxins. 

One commenter agreed with the 

proposal to remove short, paralytic 

alpha conotoxins and 

diacetoxyscirpenol. However, the 

commenter did not provide any 

rationale to why these toxins should be 

removed. The same commenter did not 

support the removal of Staphylococcal 

enterotoxins because the toxins, while 

rarely fatal, cause severe cases of food 

poisoning. Furthermore, the commenter 

stated that the toxins have been 

explored as a potential biological 

weapon during the cold war. In the 

1960’s, three different occurrences of 

laboratory exposure were reported, and 

the pathogenic dose is extremely low 

(Pinchuk et al., 2010). The commenter 

argued that the isolation of 

Staphylococcal enterotoxins is relatively 

easy and would make for a nearly 

untraceable method of bioterrorism as 

illnesses would most likely be treated as 

food poisoning due to the mishandling 

of food. HHS/CDC agreed with the 

commenter that Staphylococcal 

enterotoxins should remain as a select 

toxin because the enterotoxins can 

cause severe food poisoning and, in rare 

cases, can be fatal. Since no rationale 

was provided to remove 

diacetoxyscirpenol as a select toxin, 

HHS/CDC has decided it should be 

retained as an HHS select toxin. 

In response to the Notice of Proposed 

Rulemaking (81 FR 2805), one 

commenter supported the removal of 


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short paralytic alpha-conotoxin and one 

comment opposed the removal of short 

paralytic alpha-conotoxin. The 

commenter that opposed removal stated 

that: (1) the LD50 (lethal dose, 50% or 

median lethal dose, the amount of the 

substance required (usually per body 

weight) to kill 50% of the test 

population) of 20 mg/kg for the short 

paralytic alpha-conotoxin is not a low 

toxicity compared to other select agents, 

and this LD50 is actually in line with 

other marine toxins included on the list, 

such as Tetrodotoxin and Saxitoxin; (2) 

the LD50 of actual cone snail venom may 

be lower due to the synergistic effect of 

multiple conotoxins; and (3) conotoxins 

can be readily synthesized. The 

commenter further asserted when using 

solid phase peptide synthesis, ten grams 

of toxin is not difficult to produce. 

HHS/CDC agreed with the commenter 

and determined that conotoxins (short, 

paralytic alpha conotoxins containing 

the following amino acid sequence 

X1CCX2PACGX3X4X5X6CX7) should be 

retained as an HHS select toxin because 

the ability to produce the toxin 

synthetically is easier now with more 

modern technology. 

While HHS/CDC did not receive any 

comments regarding whether the 

exclusion amount for each toxin should 

be increased or decreased, likely due to 

insufficient evidence on LD50 levels in 

humans through various routes of 

intoxication, HHS/CDC is not proposing 

any changes to the current exclusion 

limits for the toxins, with the exception 

of short, paralytic alpha conotoxins. To 

assess the amount necessary to 

weaponize a biological toxin, the 

Department of Homeland Security 

(DHS) developed toxin parameters and 

attack scenarios for potential inhalation 

and ingestion exposures to select toxins. 

The DHS models determined the impact 

of the dissemination of varying 

concentrations of toxin on public 

health. HHS/CDC believes the amount 

of each toxin, with the exception of 

conotoxins, that could be possessed 

without regulation by a principal 

investigator, a treating physician or 

veterinarian, or a commercial 

manufacturer or distributor was 

determined on the basis of toxin 

potency and how much one could safely 

possess without constituting a potential 

threat to public safety or raising 

concerns about use as a weapon that 

would have a widespread effect. HHS/ 

CDC reviewed the LD50 used for the 

calculations and the ingestion/ 

inhalation scenarios, and the lethal 

doses of conotoxins are comparable to 

other regulated toxins with a much 

higher permissible amount. Therefore, 

HHS/CDC believes that the exclusion 

limit can be increased and still not pose 

a severe threat to public health. In 2017, 

HHS/CDC inadvertently did not propose 

an increase in the exclusion limit for 

short, paralytic alpha conotoxins in the 

Notice of Proposed Rulemaking (81 FR 

2805). Based on the DHS model, HHS/ 

CDC proposes to raise the exclusion 

limit for conotoxin from 100 mg to 200 

mg based on the toxin parameters and 

attack scenarios for potential inhalation 

and ingestion exposures to this select 

toxin. HHS/CDC would be interested in 

any comments regarding raising the 

exclusion limit from 100 mg to 200 mg. 

Please provide a detailed explanation 

for your response. 

F. Renaming Ebola Virus to the Genus 

Ebolavirus 

Recently, the International Committee 

on Taxonomy of Viruses (ICTV) 

published a report on the virus family 

Filoviridae, which classified the species 

of Ebola and Ebola-like viruses that are 

in the genus Ebolavirus (Kuhn et al., 

2019). To date, there are six species in 

the genus Ebolavirus, including Ebola 

virus, Bombali virus, Reston virus, 

Bundibugyo virus, Sudan virus, and Taı ̈

Forest virus. Currently, the HHS/CDC 

select agent list includes the name Ebola 

virus to encompass all of the six viruses 

listed above in the genus Ebolavirus. 

HHS/CDC is seeking public comment on 

whether Ebola virus, on the HHS/CDC 

select agent list as a Tier 1 select agent, 

should be renamed as Ebolavirus to 

agree with the recent taxonomic change 

by ICTV. Please provide a detailed 

explanation for your response. 

G. Designating Nipah Virus as a Tier 1 

Select Agent 

Executive Order 13546 ‘‘Optimizing 

the Security of Biological Select Agents 

and Toxins in the United States’’ 

directed the HHS Secretary to designate 

a subset of select agents and toxins that 

present the greatest risk of deliberate 

misuse with the most significant 

potential for mass casualties or 

devastating effects to the economy, 

critical infrastructure, or public 

confidence. This subset of select agents 

and toxins is identified as Tier 1. In the 

ANPRM, HHS/CDC sought public 

comment on whether Nipah virus 

should be identified as a Tier 1 select 

agent because the public health threat 

posed by Nipah virus is similar to that 

of Marburg and Ebola viruses, in terms 

of human transmissibility and high case 

fatality rate, which are both currently 

Tier 1 agents. It was also noted in the 

ANPRM that entities that are currently 

registered to possess Nipah virus are 

also in possession of other Tier 1 select 

agents. HHS/CDC received only one 

comment in support of this proposal. 

HHS/CDC is proposing Nipah virus 

should be identified as a Tier 1 select 

agent because of its: 

• Human transmissibility (person-toperson transmission has occurred) 

(Centers for Disease Control and 

Prevention, 2014; Gurley et al., 2007; 

Luby et al., 2012; and Luby et al., 2009). 

• High case fatality rate (estimated 

between 40–100%) (World Health 

Organization, 2017 and Harcourt et al., 

2004). 

• Low infectious dose (ranging from 

101–107 plaque forming units 

depending on route of infection) (DeWit 

et al., 2014; Geisbert et al., 2010; and 

Mathieu et al., 2012). 

• High severity of illness, including 

fever, headache, dizziness, vomiting, 

cough, reduced levels of consciousness, 

respiratory distress, and in some cases, 

death (Hossain et al., 2008; and Lo et al., 

2008). 

• Severe long-term effects, including 

neurological complications including 

encephalopathy, cranial nerve palsies, 

and dystonia (Sejvar et al., 2007 and Lo 

et al., 2008). These complications and 

long-term side effects in survivors of 

Nipah virus infection can also include 

persistent convulsions and personality 

changes. 

HHS/CDC would be interested in 

comments on this proposal. Please 

provide a detailed explanation for your 

response. 


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H. Adding a Footnote to the HHS Select 

Agent List 

For viruses, the International 

Committee on Taxonomy of Viruses 

(ICTV) is the international group that 

sets the standards for names of viruses. 

Commonly accepted names are still 

used in the virus community, but there 

is an effort to create a standard 

nomenclature. The committees are made 

up of virus specialists around the world 

(including from HHS/CDC specialists) to 

standardize nomenclature and work to 

avoid confusion. HHS/CDC is working 

to harmonize list of select agent viruses 

with ICTV to match the international 

standard. However, we want to ensure 

that the common names are also 

reflected (or at least captured) so if a 

name changes or is modified, then the 

list of select agent viruses is still 

accurate. As such, HHS/CDC proposes 

to add a footnote to the list for HHS 

select agents indicating that the current 

nomenclature will be available on the 

FSAP website (https://www.select

agents.gov). 

I. Discovery of Select Agents or Toxins 

Since the implementation of the select 

agent and toxin regulations in 2003 

(HHS/CDC, 2003), unless a regulatory 

exemption or exclusion is applied, 

individuals and entities are required to 

register with HHS or USDA to possess 

a select agent or toxin. Possession of 

regulated material without proper 

registration is a regulatory violation that 

could result in civil, criminal, and/or 

administrative penalties. Since this 

time, there have been at least 100 

instances of reports from entities that 

‘‘discovered’’ a select agent or toxin in 

their possession that the individual or 

entity was neither registered to possess 

as required. Many of the agents and 

toxins ‘‘discovered’’ were from studies 

associated with personnel who had left 

their entity, and the custodianship of 

samples was not reassigned. Some of the 

materials were labeled with obsolete 

pathogen names, while other 

‘‘discovered’’ material were found in 

laboratories where their active use had 

ceased, in some cases, decades prior to 

the establishment of the select agent and 

toxin regulations. 

HHS/CDC continues to receive reports 

from entities who find themselves in 

possession of select agents and toxins 

that they are not registered to possess. 

Given these instances, HHS/CDC is 

proposing to amend section 73.2 of the 

regulations to clearly state that any 

individual or entity in possession of a 

select agent or toxin, for which (1) an 

exclusion or exemption listed in 42 CFR 

part 73 does not apply, and (2) that is 

not included on a certificate of 

registration issued by the HHS Secretary 

or USDA Administrator for that 

individual or entity, must immediately 

report such possession to either the 

HHS Secretary or USDA Administrator. 

This proposal ensures that all 

discoveries of possession of a select 

agent or toxin is reported using the 

proposed new form regardless of if the 

individual or entity is registered with 

the program. As such, registered entities 

that knowingly come into possession of 

a material prior to amending their 

registration would report the possession 

using the proposed form. HHS/CDC 

would be interested in comments 

regarding the proposal to ensure the 

reporting of discovered select agents 

and toxins including if there is an 

undue burden being placed on 

registered entities to report the 

discovery as well as amending their 

registration. 

To facilitate such reporting, HHS and 

USDA plan to create, in compliance 

with the Paperwork Reduction Act, a 

new APHIS/CDC Form 6 to specify the 

information that must be submitted 

regarding the discovery of the select 

agent or toxin. Establishing a standard 

form for reporting will enable HHS and 

USDA to better understand the 

circumstances and assess regulatory 

violations related to the possession of 

‘‘discovered’’ select agents and toxins. 

J. Non-Possession of Select Agent or 

Toxin by a Registered Entity 

HHS/CDC is proposing to clarify 

throughout the regulations that 

whenever an individual or entity is 

registered to possess, use or transfer a 

select agent or toxin, the individual or 

entity is required to meet all of the 

regulatory requirements for those select 

agents and toxins listed on the 

individual or entity’s certificate of 

registration regardless of whether the 

select agent or toxin is in the actual 

possession of the individual or entity 

and without regard to the amount of 

toxin possessed. Registration permits an 

individual or entity to possess select 

agents and toxins at any time and 

indicates its readiness to do so. 

K. The Electronic Federal Select Agent 

Program (eFSAP) Information System 

HHS/CDC utilizes a highly secure 

information system, the eFSAP 

information system, to conduct all select 

agent program activities. The eFSAP 

information system is a two-way 

communication portal, which is 

accessible by both CDC and APHIS staff 

and the regulated community. For users 

at registered entities, benefits of the 

system include reduced paperwork, 

increased ease of validating and 

submitting information, and reduced 

processing time for requests (as realtime information exchange allows for 

increased responsiveness). Based on the 

implementation of the eFSAP 

information system, HHS/CDC is 

proposing to update provisions to 

indicate that reports (e.g., APHIS/CDC 

Forms 2, 3, and 4) and requests (e.g., 

amendments to registration) can be 

submitted via the eFSAP information 

system (or successor IT system as 

specified by CDC in guidance). In 

addition, the electronic documentation 

in the eFSAP information system serves 

as official records required by the select 

agent and toxin regulations, and once 

submitted in the eFSAP information 

system, there is no requirement for 

entities to retain a separate copy. 

L. Registration 

The certificate of registration is the 

document issued by the Federal Select 

Agent Program to an individual or entity 

that denotes approval to possess, use 

and/or transfer specified select agents 

and toxins; the specific activities related 

to the registered select agents and/or 

toxins; persons authorized to access the 

select agents and/or toxins; and the 

locations (buildings, rooms, suites of 

rooms, storage facilities, etc.) where 

select agents and/or toxins are 

authorized to be present as described in 

the individual or entity’s APHIS/CDC 

Form 1. The issuance of a certificate of 

registration may be contingent upon 

inspection or submission of additional 

information, such as the security plan, 

biosafety plan, incident response plan, 

or any other documents required to be 

prepared to meet requirements of the 

select agent and toxin regulations. In 

addition, the certificate of registration is 

required to be amended prior to making 

any changes and must be reauthorized 

at least every three years from the date 

it was initially issued or renewed. The 

individual or entity’s certificate of 

registration must be amended to reflect 

changes in circumstances relative to the 

possession and use of select agent and 

toxins (e.g., replacement of the 

Responsible Official or other personnel 

changes, changes in ownership or 

control of the individual or entity, 

changes in the locations and activities 

involving any select agents or toxins, or 

the addition or removal of select agents 

or toxins). As such, HHS/CDC is 

proposing clarification to language to 

explain that an amendment ‘‘must’’ be 

submitted instead of ‘‘may’’ for any 

changes to the approved certificate of 

registration. The proposal corrects a 

discrepancy between language found in 

(i) that states an amendment may be 


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submitted versus language found in 

(i)(1), which states that the Responsible 

Official must apply for amendment. An 

entity must submit an amendment prior 

to making any change. Therefore, the 

use of ‘‘may’’ is not an accurate term. 

With the use of eFSAP information 

system instead of the submission of a 

revised form, HHS/CDC proposes to 

update language to replace ‘‘additional 

documents’’ to ‘‘additional information’’ 

since information is what is being 

revised in the system and not 

documents. 

M. Tier 1 Security Enhancements 

HHS/CDC is proposing to clarify 

security enhancements regarding 

screening visitors for those entities 

possessing Tier 1 select agents and 

toxins because HHS/CDC believes the 

new language clearly specifies the 

requirements and will aid in 

compliance. The proposed provision 

has been revised to read: ‘‘Entities with 

Tier 1 select agents and toxins must 

prescribe the following security 

enhancements: Procedures for screening 

visitors, their property, and, where 

appropriate, vehicles at entry and exit 

points to registered space based on the 

entity’s site-specific risk assessment.’’ 

While HHS/CDC does not have any 

evidence of non-compliance, HHS/CDC 

has received feedback from the 

registered entities requesting 

clarification on the current provision 

that reads: ‘‘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.’’ 

HHS/CDC believes the proposed 

provision will clarify there are multiple 

checkpoints needed to ensure 

compliance with the Tier 1 requirement. 

N. Biosafety—Facility Verification 

HHS/CDC is proposing to require 

facility verification every 12 months for 

registered entities that maintain 

biosafety level 3 and animal biosafety 

level 3 laboratories. The proposal is to 

codify the 2014 policy that provided 

specific provisions for the verifications 

regarding BSL–3/ABSL–3 facilities to 

meet the requirements outlined under 

42 CFR 73.12(b) ‘‘biosafety and 

containment procedures must be 

sufficient to contain the select agent or 

toxin (e.g., physical structure and 

features of the entity, and operational 

and procedural safeguards).’’ The 

verifications also must be documented 

and validate the facility’s containment 

functions such as inward directional 

airflow, decontamination systems, and 

preventative maintenance. Therefore, 

HHS/CDC is proposing to require the 

entity to document facility verification 

and require the entity to verify the 

facility’s containment functions. 

HHS/CDC does not believe that the 

new provisions will create an additional 

burden to entities that maintain 

biosafety level 3 and animal biosafety 

level 3 laboratories since these entities 

are already performing annual facility 

verifications. However, if a registered 

entity has not been performing annual 

facility verifications for biosafety level 3 

and animal biosafety level 3 

laboratories, HHS/CDC would be 

interested in comments concerning the 

cost and burden of annual facility 

verifications, especially if the entity is 

considered a small business. 

O. Biosafety—Effluent Decontamination 

System 

Biosafety level 3 and biosafety level 4 

facilities are highly sophisticated 

facilities built to contain biological 

agents and toxins with the highest 

potential to threaten agricultural, plant 

and public health and safety. Any 

defect, such as a crack or leaky pipe, 

could have severe consequences. In 

August 2007, foot-and-mouth disease 

was discovered at farms in the United 

Kingdom. The source of the 

contamination was determined to be 

long-term damage and leakage of a 

drainage system used by a highcontainment laboratory working with 

the foot-and-mouth disease virus. Given 

these risks, HHS/CDC is proposing to 

amend the security, biosafety, and 

incident response sections of the select 

agents and toxins regulations to address 

risks posed by the effluent 

decontamination systems used by 

biosafety level 3 and biosafety level 4 

facilities. 

If an effluent decontamination system 

is used by an entity, the entity must 

include in its plans how it will address 

security, biosafety, and incident 

response as it relates to the system. 

Specifically, the biosafety plan must 

provide for verification that the liquid 

waste generated from registered space is 

sufficiently treated to prevent the 

release of a select agent or toxin prior 

to discharge of the waste from the 

facility. The security plan, for any space 

not listed on the entity’s registration 

that contains a portion of an effluent 

decontamination system, must describe 

procedures to prevent the theft, loss, or 

unauthorized access to a select agent or 

toxin. The incident response plan must 

fully describe the entity’s response 

procedures for the theft, loss, or release 

of a select agent or toxin; the failure of 

an effluent decontamination system 

resulting in a release of a select agent or 

toxin, and how personnel will access an 

area potentially containing a select 

agent or toxin due to the failure of an 

effluent decontamination system. 

P. Restricted Experiments 

HHS/CDC proposes to clarify the 

provision that the receiving entity must 

amend their certificate of registration 

and receive approval by CDC or APHIS 

to possess the products of a restricted 

experiment. Entities are currently 

required to obtain approval to conduct 

restricted experiments and possess the 

product of a select agent or toxin that 

results from a restricted experiment. 

However, the current provisions do not 

address if the entity comes into 

possession of a product of a restricted 

experiment based on the transfer of the 

agent. This proposal aligns with the 

registration section where the 

Responsible Official must apply for an 

amendment and receive approval prior 

to any change in the registration, such 

as the receipt of a product of a restricted 

experiment. The proposed provisions 

also ensure receiving entities have the 

appropriate safeguards in place to 

receive and possess the product from a 

transfer. 

Q. Training 

HHS/CDC is proposing revisions to 

the training requirements in accordance 

with the new mandate in the Prepare for 

and Respond to Existing Viruses, 

Emerging New Threats, and Pandemics 

Act (42 U.S.C. 262a(k)(1); Pub. L. 117– 

328). These revisions have been made in 

an effort to comply with the statutory 

amendment that states training 

requirements for (1) unapproved 

individuals whose responsibilities 

routinely place them in close proximity 

to laboratory facilities and (2) those 

individuals who perform administrative 

or oversight functions. Trainings must 

be completed within 6 months after the 

final rule is published. 

R. Records 

HHS/CDC proposes to clarify the 

records provisions to ensure accurate, 

current inventory is maintained for each 

select agent held in long-term storage 

and all toxins to more clearly specify 

the requirements and aid in compliance. 

HHS/CDC is proposing that records 

contain: (1) the quantity acquired and 

the name of the individual by whom the 

select agent or toxin was acquired; (2) 

the location where it is stored (e.g., 

building, room number or name, and 

freezer identification or other storage 

container); (3) for removal and return of 

the select agent or toxin from storage, 

the date the select agent or toxin was 


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removed and returned, the purpose for 

using it, the name of the individual who 

removed and returned it, and when 

applicable, date of final disposition of 

the select agent or toxin and by whom; 

and (4) for intra-entity transfers (sender 

and the recipient are covered by the 

same certificate of registration), name of 

the select agent or toxin, the date of the 

transfer, the number of items or quantity 

of the select agent or toxin transferred, 

the name of the sender, and the name 

of the recipient. HHS/CDC believes the 

proposed provision will clarify 

information needed to ensure the 

inventory is accurate and complete from 

the select agents and toxins origination 

to destruction. Due to prior inquiries 

received from the regulated community, 

HHS/CDC is seeking comments on 

whether the proposed changes are 

specific enough to ensure proper 

records are maintained. 

S. Codifying Existing Policies 

HHS/CDC is proposing to incorporate 

five existing policies previously 

published and found at 

www.selectagents.gov into regulations 

and are soliciting public comments on 

these policies, further discussed below. 

By codifying these existing policies into 

regulation, HHS/CDC aims to provide 

clarity and stability in program 

requirements, make compliance more 

straight-forward for regulated entities, 

and ensure enforcement is consistent 

and predictable across the regulated 

community. 

1. Conclusion of Patient Care 

HHS/CDC proposes to codify in 

regulation the current policy that for an 

individual who has been admitted to a 

medical facility, the ‘‘conclusion of 

patient care’’ and the point when 

‘‘delivery of patient (i.e., human) care by 

heath care professionals has concluded’’ 

is when an individual is no longer 

receiving treatment provided by the 

medical facility or physician. If the 

patient is seen by the physician or 

medical facility for follow-up care (e.g., 

six-month follow-up visit), this would 

be considered a new delivery of patient 

care. 

The policy also clarified that select 

agent waste generated during the 

delivery of patient care applies only to 

the treatment of humans. Accordingly, 

specimens or waste associated with that 

individual (e.g., tissue samples, body 

fluids, fomites and any other 

contaminated material likely to transmit 

an infection to people through the 

environment if it is unable to be 

decontaminated) must be destroyed or 

transferred to a registered individual or 

entity within seven days after an 

individual is no longer receiving 

treatment provided by the medical 

facility. 

2. When Animals Naturally Infected 

With Select Agents Are Excluded 

HHS/CDC proposes to codify in 

regulation the current policy regarding 

when animals naturally infected with 

select agents are excluded from the 

requirements of the regulations. 

Sections 73.3(d)(1) and 73.4(d)(1) 

provide for exclusion of select agents 

occurring in their natural environment. 

Mere possession of an animal that is 

naturally infected with a select agent, 

either within its natural environment or 

having been transported to an 

artificially established environment, 

meets the criteria of this exclusion. 

However, the removal of an animal 

which is naturally infected with a select 

agent from its natural environment to an 

artificially established environment for 

the purpose of 

(1) the intentional exposure or 

introduction of a select agent to a naı ̈ve 

or experimental animal; or 

(2) the introduction of a naı ̈ve animal 

to a natural environment where there is 

an animal that is naturally infected with 

a select agent for the purpose of the 

intentional exposure or introduction of 

a select agent to the naı ̈ve or 

experimental animal, does not meet the 

exclusion criteria. 

If an animal is confirmed to be 

naturally infected with a select agent, 

there may be additional transfer and/or 

transport restrictions based upon other 

federal or state requirements. 

3. Inactivation 

HHS/CDC proposes to codify into 

regulation the current policies regarding 

inactivation, clarifying and reorganizing 

the existing provisions regarding select 

agent inactivation and select agent 

removal, and clarifying that a certificate 

must be generated prior to excluding 

inactivated or select agent-free material. 

For chemical inactivation of whole 

tissue or homogenized tissue, two 

options are acceptable when choosing 

appropriate tissue for procedure 

validation. The first option is to use the 

tissue that is expected to have the 

highest concentration of the specific 

agent to serve as a surrogate for other 

tissues, including those in other animal 

models, so long as all standardized 

conditions (e.g., the agent used, tissue 

volume, and ratio of tissue to volume of 

inactivating chemical) are held constant. 

The second option is to determine the 

agent concentration in a tissue before 

performing the inactivation procedure 

and set this concentration as the 

maximum agent limit for subsequent 

inactivation procedures. A safety margin 

must be incorporated into the final 

chemical inactivation procedure to 

ensure the effective inactivation of the 

agent. 

Any select agent or regulated nucleic 

acid that can produce infectious forms 

of any select agent virus is excluded if 

the material is contained in a formalinfixed paraffin-embedded tissue or fixed 

to slides (e.g., Gram stain) that have 

been effectively inactivated by a 

recognized method for that particular 

agent or regulated nucleic acid. HHS/ 

CDC also proposes to codify the policy 

that allows individuals approved by 

HHS or USDA to access select agents 

and toxins besides the Responsible 

Official (e.g., Principal Investigators) to 

revise the inactivation procedures, if 

necessary. Principal investigator is 

defined in the regulations as the one 

individual who is designated by the 

entity to direct a project or program and 

who is responsible to the entity for the 

scientific and technical direction of that 

project or program. When a Principal 

investigator is unavailable (such as out 

of the office) to review the results of a 

select agent that has been subjected to 

a validated inactivation or removal 

procedure, a temporary designee 

(appointed by the principal investigator 

and approved of by the responsible 

official) may sign the inactivation 

certificate to allow for work to continue. 

The temporary designee must be listed 

on the entity’s registration and have the 

knowledge and expertise to provide 

scientific and technical direction 

regarding the validated inactivation 

procedure or the procedure for removal 

of viable select agent to which the 

certificate refers. The appointment of a 

designee to sign certificates is not for 

regular substitution of the principal 

investigator, such as the principal 

investigator relinquishing this 

requirement to other individuals in the 

laboratory due to normal work demands 

or general unavailability. In addition, 

HHS/CDC is proposing to codify in 

regulation the current policies regarding 

records for inactivated or select agentfree material, to clarify what records are 

needed for inactivated or select agentfree material (to include allowance of a 

knowledgeable designee to sign the 

certificate of inactivation on behalf of a 

Principal Investigator during his/her 

absence, a timeframe after inactivation 

or select agent removal for when 

certificates must be signed and for how 

long they must be kept by the entity), 

and a requirement that certificates 

accompany all transfers including intraentity transfers. These proposed 

provisions clarify the recordkeeping 


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requirements regarding inactivation 

procedures and inactivated or select 

agent-free material. It also allows 

Principal Investigators to designate 

individuals to sign on their behalf 

within seven days after completion of 

the validated inactivation or validated 

viable select agent removal, and require 

a certificate to be maintained for as long 

as the material is in the possession of 

the registered individual or entity plus 

an additional 3 years. The inclusion of 

the policies into the regulations verifies 

the material has been inactivated by the 

subject matter expert and the 

verification document is available 

throughout its possession by the entity. 

4. Responsible Official and Alternate 

Responsible Official 

HHS/CDC proposes to codify in 

regulation the current policy that the 

Responsible Official (RO) cannot be 

approved as RO at more than one 

registered individual or entity. We also 

propose to clarify the policy that a RO 

cannot be approved to be the sole 

Alternate Responsible Official (ARO) at 

another registered individual or entity. 

This means that the RO can serve as 

ARO at another registered individual or 

entity as long as they are not the only 

ARO at the other individual or entity. In 

addition, HHS/CDC proposes to codify 

in regulation that an individual who has 

been approved as an ARO at one 

individual or entity can be approved to 

be an ARO at another registered 

individual or entity. The 2017 policy 

statement regarding Approval of a 

person to be a Responsible Official at 

only one entity, was necessary and was 

based on the federal regulations that 

specify that the RO must ‘‘have a 

physical (and not merely a telephonic or 

audio/visual) presence at the registered 

entity to ensure that the entity is in 

compliance with the select agent 

regulations and 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.’’ 

5. Annual Internal Inspections 

HHS/CDC proposes to codify in 

regulation the current policy that an 

individual or entity’s annual internal 

inspections must address whether: 

1. The individual or entity’s biosafety/ 

biocontainment plan is being effectively 

implemented, as outlined in Section 12. 

2. The individual or entity’s security 

plan is being effectively implemented, 

as outlined in Section 11. 

3. The individual or entity’s incident 

response plan is implemented to ensure 

whether the entity is able to respond, as 

outlined in Section 14. 

4. Each individual with access 

approval from the HHS Secretary or 

Administrator has received the 

appropriate training as outlined in 

Section 15. 

The proposal codified the 2019 policy 

that clarified the language of section 9 

(a) based on the HHS’ Office of 

Inspector General’s Report, ‘‘Entities 

Generally Met Federal Select Agent 

Program Internal Inspection 

Requirements But CDC Could Do More 

To Improve Effectiveness’’ (OEI–04–15– 

00431) recommendation ‘‘to clarify to 

DSAT inspectors and to entities the 

breadth and depth required for internal 

inspections, including which of the 

regulatory sections and subsections of 

42 CFR part 73 must be addressed as 

inspection standards.’’ 

IV. Alternatives Considered 

One alternative to the proposed rule 

considered by HHS was not to propose 

to codify the current operational 

policies listed above and to propose the 

delisting of the select agents. However, 

we decided to propose codification for 

the sake of consistency with USDA and 

transparency with our stakeholders. The 

proposed changes are currently 

operationalized, and codification of the 

policies has been recommended by 

various governmental entities. Without 

codification we would not have 

transparency and consistency 

throughout agencies which is important 

when requiring strict adherence to our 

proposed regulatory policies for select 

agents; thus, we have rejected the 

alternative to not codify our operational 

policies that are closely coordinated 

between USDA and HHS. Moving 

forward with codifying the current 

operational policies listed above and not 

proposing to delist the select agents 

through federal notice would not be 

meeting the regulatory mandate under 

42 U.S.C. 262a(a)(2) where the HHS 

Secretary must review and republish the 

list of HHS select agents and toxins at 

least biennially. 

V. Required Regulatory Analyses 

A. Executive Orders 12866, 13563, and 

14094 

HHS/CDC has examined the impacts 

of the NPRM under Executive Order 

12866, Regulatory Planning and Review 

(58 FR 51735, October 4, 1993) and 

Executive Order 13563, Improving 

Regulation and Regulatory Review, (76 

FR 3821, January 21, 2011). Both 

Executive Orders direct agencies to 

evaluate any rule prior to promulgation 

to determine the regulatory impact in 

terms of costs and benefits to United 

States populations and businesses. 

Further, together, the two Executive 

Orders set the following requirements: 

quantify costs and benefits where the 

new regulation creates a change in 

current practice; qualitatively describe 

costs and benefits; choose approaches 

that maximize net benefits; and support 

regulations that protect public health 

and safety. HHS/CDC has analyzed the 

NPRM as required by these Executive 

Orders and has determined that it is 

consistent with the principles set forth 

in the Executive Orders and the 

Regulatory Flexibility Act, as amended 

by the Small Business Regulatory 

Enforcement Fairness Act (SBREFA). 

Executive Order 12866, as reaffirmed 

by E.O. 13563 and E.O. 14094, provides 

that the Office of Information and 

Regulatory Affairs (OIRA) in the Office 

of Management and Budget will review 

all significant rules. OIRA has 

determined that this rule is significant. 

Executive Order 14094 reaffirms the 

principles of E.O. 12866 and E.O. 13563 

and states that regulatory analysis 

should facilitate agency efforts to 

develop regulations that serve the 

public interest, advance statutory 

objectives, and are consistent with E.O. 

12866, E.O. 13563, and the Presidential 

Memorandum of January 20, 2021 

(Modernizing Regulatory Review). 

Regulatory analysis, as practicable and 

appropriate, shall recognize distributive 

impacts and equity, to the extent 

permitted by law. We have developed 

this proposed rule in a manner 

consistent with these requirements. E.O. 

13563 emphasizes further that 

regulations must be based on the best 

available science and that the 

rulemaking process must allow for 

public participation and an open 

exchange of ideas. We have developed 

this proposed rule in a manner 

consistent with these requirements. In 

administering the Federal Select Agent 

Program (FSAP), HHS, along with 

USDA, regularly interact with the 

affected registered entities via email, 

phone, online webinars, and 

interactions through the eFSAP 

information system and through 

registered entity designated points of 

contact. All proposed changes are being 

proposed as a direct result of entity 

questions received and/or interaction 

with registered entities who have 

contacted FSAP when they had 

questions or regulatory interpretation 

requests. Therefore, HHS/CDC believes 

this proposed rule serves the public 

interest. Additionally, HHS/CDC further 

encourages public participation and will 

inform registered entities of this 

proposed rule via a Select Agent (SA) 

Gram to ensure they are aware that they 

have a chance to provide public 


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5834 Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 

comments. The proposed rule will also 

be communicated to the general public 

via a GovD message to ensure the public 

has a chance to review and provide 

comments. The Federal Select Agent 

Program website (www.selectagents.gov) 

will also be updated to share what the 

proposed changes are and will provide 

a link to web visitors so that they can 

review and provide comments on our 

Federal Register notice. Lastly, outreach 

notes summarizing the proposed rule 

will be emailed directly to national 

partner organizations (The Association 

of Public Health Laboratories, American 

Society for Microbiology, American 

Biological Safety Association, etc.) so 

that they can share among their 

constituents. 

We have prepared an economic 

analysis for this NPRM. The economic 

analysis provides a cost-benefit analysis, 

as required by Executive Order 12866. 

This regulatory flexibility analysis also 

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 at the Supporting Materials tab 

of the docket, or at www.select 

agents.gov. 

Summary of the Regulatory Impact 

Analysis 

HHS/CDC has proposed modifications 

to the list of select agents and toxins as 

well as revisions to several of the select 

agent and toxin regulations. These 

proposed revisions to the select agent 

and toxin regulations will increase their 

usability as well as provide for 

enhanced program oversight. 

Specifically, HHS/CDC is proposing to 

add definitions for several terms 

(Discovery, Theft, Loss, Release, 

Validated Removal Procedure, 

Verification viability testing protocol); 

codify policies regarding the role of 

responsible officials and alternate 

responsible officials, conclusion of 

patient care, and annual internal 

inspections; and revise or clarify 

provisions related to validated 

inactivation procedures and viable 

select agent removal methods, 

recordkeeping, non-possession of select 

agents and toxins, eFSAP, registration, 

Tier 1 enhancements, and exclusion of 

naturally infected animals. HHS/CDC is 

also proposing to add requirements for 

reporting discoveries of select agents 

and toxins, provisions regarding effluent 

decontamination system, biosafety 

provisions for facility verification 

requirements for registered biosafety 

level 3 and animal biosafety level 3 

laboratories, new requirement related to 

restricted experiments, as well as to 

correct editorial errors. These proposed 

changes would economically benefit 

producers, research and reference 

laboratories, and State and Federal 

oversight agencies, while also 

maintaining adequate program oversight 

of select agents and toxins. 

Currently, there are 236 entities 

registered with APHIS and CDC. Of 

these entities, there are 13 Private 

entities, 30 Federal entities, 42 

Commercial entities, 84 Academic 

entities, and 67 State entities registered 

with APHIS and CDC. Less than 4 

percent of all firms operating within 

these North American Industry 

Classification (NAICS) categories are 

considered to be small entities. The 

NPRM will not have a significant 

economic impact on a substantial 

number of small entities. 

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 proposed amendments to the 

regulations will enhance the protection 

of human, animal, and plant health and 

safety. The proposal is to 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. 

B. The Regulatory Flexibility Act (RFA), 

as Amended by the Small Business 

Regulatory Enforcement Fairness Act 

(SBREFA) 

HHS/CDC has examined the impacts 

of the proposed rule under the 

Regulatory Flexibility Act (5 U.S.C. 

601–612). Unless HHS/CDC certifies 

that the proposed rule is not expected 

to have a significant economic impact 

on a substantial number of small 

entities, the Regulatory Flexibility Act 

(RFA), as amended by the Small 

Business Regulatory Enforcement 

Fairness Act (SBREFA), requires 

agencies to analyze regulatory options 

that would minimize any significant 

economic impact of a rule on small 

entities. HHS/CDC certifies that this 

proposed rule will not have a significant 

economic impact on a substantial 

number of small entities within the 

meaning of the RFA. 

This regulatory action is not a major 

rule as defined by Sec. 804 of the Small 

Business Regulatory Enforcement 

Fairness Act of 1996. This proposed rule 

will not result in an annual effect on the 

economy of $100,000,000 or more; a 

major increase in cost or prices; or 

significant adverse effects on 

competition, employment, investment, 

productivity, innovation, or on the 

ability of United States-based 

companies to compete with foreignbased companies in domestic and 

export markets. 

C. Paperwork Reduction Act of 1995 

In accordance with section 3507(d) of 

the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501 et seq.), HHS/CDC has 

determined that the Paperwork 

Reduction Act does apply to 

information collection and 

recordkeeping requirements included in 

this rule. HHS/CDC notes that the 

information collection and 

recordkeeping requirements are already 

approved by the Office of Management 

and Budget (OMB) under OMB Control 

Number 0920–0576, expiration 1/31/ 

2024. HHS/CDC will be seeking renewal 

of the information collection prior to the 

publication of the final rule. HHS/CDC 

will also pursue OMB approval for the 

proposed Form 6 through a separate 

process, through a standard clearance 

with OMB, rather than in this 

rulemaking. 

The total estimated annualized 

burden for all data collection was 

calculated using the 2021 Annual 

Report of the Federal Select Agent 

Program available at https://www.select

agents.gov/resources/publications/ 

annualreport/2021.htm or FSAP IT 

system and is estimated as 3,655.5 hours 

and includes additional 30 minutes 

added to the average burden per 

response (in hours) for the training 

proposal in accordance with the new 

mandate in the Consolidated 

Appropriations Act, 2023, Public Law 

117–328 (division H, title II, section 

2311), ‘‘Improving Control and 

Oversight of Select Biological Agents 

and Toxins’’ (Section 351A of the Public 

Health Service Act (42 U.S.C. 262a)) 

amendment of subsection (b)(1). 

Information will be collected through 

FSAP IT system, fax, email and hard 

copy mail from respondents. 


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Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 5835 

ESTIMATED ANNUALIZED BURDEN HOURS

Section Form name Number of 

respondents 

Number of 

responses per 

respondent 

Average burden 

per response 

(in hours) 

Total 

burden 

hours 

Sections 3 & 4 ....... Request for Exclusions ....................................................... 1 1 1 1 

Sections 5 & 6 ....... Form 4—Report of Identification of a Select Agent or 

Toxin.

917 1 1 917 

Sections 5 & 6 ....... Form 5—Request of Exemption .......................................... 1 1 1 1 

Section 7 ................ Form 1—Application for Registration .................................. 5 1 5 25 

Section 7 ................ Form 1 Sec 6A—Amendment to a Certificate of Registration.144 5 1 720 

Section 9 ................ Documentation of self-inspection ........................................ 233 1 1 233 

Section 10 .............. Request for Expedited Review ............................................ 1 1 30/60 1 

Section 11 .............. Security Plan ....................................................................... 233 1 1 233 

Section 12 .............. Biosafety Plan ..................................................................... 233 1 1 233 

Section 13 .............. Request Regarding a Restricted Experiment ..................... 3 1 2 6 

Section 14 .............. Incident Response Plan ...................................................... 233 1 1 233 

Section 15 .............. Training ................................................................................ 233 1.5 1.5 339.5 

Section 16 .............. Form 2—Request to Transfer Select Agents and Toxins ... 229 1 1.5 380 

Section 17 .............. Records ............................................................................... 233 1 30/60 117 

Section 19 .............. Form 3—Notification of Theft, Loss, or Release ................ 185 1 1 185 

Section 20 .............. Administrative Review ......................................................... 22 1 1 22 

Total ................ .............................................................................................. .................... ........................ .......................... 3,655.5 

D. E.O. 12988: Civil Justice Reform 

This rule has been reviewed under 

E.O. 12988, Civil Justice Reform. Once 

the final rule is in effect, HHS/CDC 

notes that: (1) All State and local laws 

and regulations that are inconsistent 

with this rule will be preempted; (2) No 

retroactive effect will be given to this 

rule; and (3) Administrative proceedings 

will not be required before parties may 

file suit in court challenging this rule. 

E. E.O. 13132: Federalism 

HHS/CDC has reviewed this proposed 

rule in accordance with Executive Order 

13132 regarding Federalism and has 

determined that it does not have 

‘‘federalism implications.’’ The rule 

does not ‘‘have substantial direct effects 

on the States, on the relationship 

between the national government and 

the States, or on the distribution of 

power and responsibilities among the 

various levels of government.’’ 

In accordance with section 361(e) of 

the PHSA [42 U.S.C. 264(e)], nothing in 

this rule would supersede any 

provisions of State or local law except 

to the extent that such a provision 

conflicts with this rule. 

F. Plain Language Act of 2010 

Under the Plain Language Act of 2010 

(Pub. L. 111–274, October 13, 2010), 

executive Departments and Agencies are 

required to use plain language in 

documents that explain to the public 

how to comply with a requirement the 

Federal Government administers or 

enforces. HHS/CDC has attempted to 

use plain language in promulgating this 

rule consistent with the Federal Plain 

Writing Act guidelines. 

VI. References 

Abdu F. Pathogenic Rickettsiae as 

Bioterrorism Agents, Clinical Infectious 

Diseases, 45 (Supplement_1). 2007. p. 

S52–S55. 

Adler M. et al. Toxicity of Botulinum 

Neurotoxin by Inhalation: Implications 

in Bioterrorism. In: Salem H, Katz SA, 

editors. Aerobiology: The Toxicology of 

Airborne Pathogens and Toxins. 

Cambridge: The Royal Society of 

Chemistry Press; 2016. p. 167–82. 

Anderson A. et al. Seroprevalence of Q fever 

in the United States, 2003–2004. Am J 

Trop Med Hyg. 2009. 81: p. 691–694. 

Battisti, L. et al. Mating system for transfer 

of plasmids among Bacillus anthracis, 

Bacillus cereus, and Bacillus 

thuringiensis. J Bacteriol. 1985. 162(2): p. 

543–50. 

Bergdoll, M. Staphylococcal intoxications, in 

Foodborne infections and intoxications, 

2nd Edition, H. Riemann and F.L. Bryan, 

Editors. 1979, Academic Press. 

Biodefence Modeling Parameter Review 

Workshop. 2013: Ventura, California. 

Cataldi A., et al. Characterization of Bacillus 

anthracis strains used for vaccination. 

2000. J Appl Microbiol 86: p. 648–654. 

Centers for Disease Control and Prevention. 

2017. Annual U.S. Hantavirus Disease 

and HPS Case Fatality, 1993–2016. 

Retrieved from https://www.cdc.gov/ 

hantavirus/surveillance/annualcases.html. 

Centers for Disease Control and Prevention 

and National Institutes of Health. 2009. 

Biosafety in Microbiological and 

Biomedical Laboratories. 5th ed. 

Retrieved from https://www.cdc.gov/ 

labs/pdf/CDC-BiosafetyMicrobiological

BiomedicalLaboratories-2009-P.PDF. 

Cross, et al. Zoonoses under our noses. 

Microbes and Infection, 2019. 21(1). 

https://doi.org/10.1016/ 

j.micinf.2018.06.001 

Cutler, S. Q Fever. J Infect, 2007. 54(4): p. 

313–8. 

De Wit, E., et al. Foodborne transmission of 

Nipah virus in Syrian Hamsters. PLoS 

Pathog, 2014. 10(3): p. e1004001. 

Eremeeva, M. E. et al. Typhus, Epidemic 

(Rickettsia prowazekii) and Rocky 

Mountain Spotted Fever (Rickettsia 

rickettsii). Encyclopedia of Bioterrorism 

Defense, 2005. John Wiley & Sons, Inc. 

Gardner, C., et al., Eastern and Venezuelan 

equine encephalitis viruses differ in their 

ability to infect dendritic cells and 

macrophages: impact of altered cell 

tropism on pathogenesis. J Virol. 2008. 

82(21): p. 10634–46. 

Geisbert, T., et al. Development of an Acute 

and Highly Pathogenic Nonhuman 

Primate Model of Nipah Virus Infection. 

PLoS ONE, 2010. 5(5): p. e10690. 

Gidding H., et al. Q fever seroprevalence in 

Australia suggests one in twenty people 

have been exposed. Epidemiol Infect. 

2020. 148: e18. 

Godfroid, J., et al. Brucellosis in Terrestrial 

Wildlife. Rev sci tech Off int Epiz. 2013. 

32(1), p. 27–42. 

Green, B., et al. Involvement of Tn4430 in 

transfer of Bacillus anthracis plasmids 

mediated by Bacillus thuringiensis 

plasmid pXO12. J Bacteriol. 1989. 

171(1): p. 104–13. 

Gurley, E., et al. Person-to-Person 

Transmission of Nipah virus in a 

Bangladeshi Community. Emerg Infect 

Dis, 2007. 13(7): p. 1031–7. 

Guzman, K.D., et al., Biological Terrorism 

Modeling Parameters. 2014, Sandia 

National Laboratories. 

Harcourt, B., et al. Genetic Characterization 

of Nipah virus, Bangladesh, 2004. Emerg 

Infect Dis, 2005. 11(10): p. 1594–1597. 

HHS/CDC. November 3, 2003. Possession, 

Use, and Transfer of Select Agents and 

Toxins. Interim Final Rule. https://www.

federalregister.gov/d/03-27659. 


khammond on DSKJM1Z7X2PROD with PROPOSALS
5836 Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 

Hossain, M., et al. Clinical Presentation of 

Nipah virus Infection in Bangladesh. 

Clin Infect Dis, 2008. 46(7): p. 977–84. 

Institute for International Cooperation in 

Animal Biologics. 2004. Typhus FeverRickettsia prowazekii. Retrieved from 

http://www.cfsph.iastate.edu/Factsheets/ 

pdfs/typhus_fever.pdf. 

Ivins, B., et al. Immunization Studies with 

Attenuated Strains of Bacillus anthracis. 

Infect Immun, 1986. 52(2):p. 454–458. 

Johnston, C., et al. Bacterial Transformation: 

Distribution, Shared Mechanisms and 

Divergent Control. Nature Rev. 

Microbiol, 2014. 12: p. 181–196. 

Kersh G., et al. Presence of Coxiella burnetii 

DNA in the environment of the United 

States, 2006 to 2008. Appl Environ 

Microbiol. 2010. 

Kinney, R., et al., Attenuation of Venezuelan 

equine encephalitis virus strain TC–83 is 

encoded by the 5’-noncoding region and 

the E2 envelope glycoprotein. J Virol, 

1993. 67(3): p. 1269–77. 

Knutsen, H., et al. Risk to human and animal 

health related to the presence of 4,15- 

diacetoxyscirpenol in food and feed. 

EFSA Jour, 2018. 16(8): p. 1–106. 

Koehler, T., et al. Bacillus subtilis (natto) 

plasmid pLS20 mediates interspecies 

plasmid transfer. J Bacteriol. 1987. 

169(11): p. 5271–8. 

Kuhn, J., et al. ICTV Virus Taxonomy Profile: 

Filoviridae. J Gen Virol. 2019. 100(6): p. 

911–912. 

Lo, M., et al. The Emergence of Nipah virus, 

a Highly Pathogenic Paramyxovirus. J 

Clin Virol, 2008. 43(4): p. 396–400. 

Luby, S., et al. Epidemiology of Henipavirus 

disease in Humans. Curr Top Microbiol 

Immunol, 2012. 359: p. 25–40. 

Luby, S., et al. Recurrent Zoonotic 

Transmission of Nipah virus into 

Humans, Bangladesh, 2001–2007. Emerg 

Infect Dis, 2009. 15(8): p. 1229–35. 

Luna, V., et al. Bacillus anthracis Virulent 

Plasmid pXO2 Genes Found in Large 

Plasmids of Two Other Bacillus species. 

J of Clinical Microbiol, 2006. 44(7): P. 

2367–77. 

Mathieu, C., et al. Nonstructural Nipah Virus 

C Protein Regulates both the Early Host 

Proinflammatory Response and Viral 

Virulence. Journal of Virology, 2012. 

86(19): p. 10766–10775. 

Olsen, S., et al. Biosafety Concerns Related to 

Brucella and its Potential Use as a 

Bioweapon. Applied Biosafety, 2018. 

23(2): p. 77–90. 

Paessler, S., et al., Vaccines for Venezuelan 

equine encephalitis. Vaccine, 2009. 27 

Suppl 4: p. D80–5. 

Peck, M., Biology and genomic analysis of 

Clostridium botulinum. Adv Microb 

Physiol, 2009. 55: p. 183–265, 320. 

Pike, R. Laboratory-Associated Infections: 

Summary and Analysis of 3921 Cases. 

Health Lab Sci, 1976. 13(2): p. 105–14. 

Puig de Centorbi, O., et al. Selection of a 

Strain of Clostridium argentinense 

Producing High Titers of Type G 

Botulinal Toxin. Zentralbl Bakteriol. 

1997. 286(3): p. 413–9. 

Raoult, D., et al. Antimicrobial Therapy of 

Rickettsial Diseases. Antimicrob Agents 

Chemother, 1991. 35(12): p. 2457–62. 

Reynolds, M.G., et al., Flying SquirrelAssociated Typhus, United States. Emerg 

Infect Dis, 2003. 9(10): p. 1341–3. 

Rivas, F., et al. Epidemic Venezuelan Equine 

Encephalitis in La Guajira, Colombia. J 

Infect Dis, 1997. 175(4): p. 828–32. 

Rolain, J., et al. Correlation Between Ratio of 

Serum Doxycycline Concentration to 

MIC and Rapid Decline of Antibody 

Levels during Treatment of Q Fever 

Endocarditis. Antimicrob Agents 

Chemother, 2005. 49: p. 2673–76. 

Rossi, S., et al. Rationally Attenuated 

Vaccines for Venezuelan Equine 

Encephalitis Protect Against Epidemic 

Strains with a Single Dose. Vaccines, 

2020. 8(3): p. 497. 

Ruhfel et al. Interspecies transduction of 

plasmids among Bacillus anthracis, B. 

cereus, and B. thuringiensis. J Bacteriol, 

1984. 157(3): p.708–11. 

Shakir, R. Brucellosis. Journal of the 

Neurological Sciences, 2021. 420(15). 

https://doi.org/10.1016/j.jns.2020.117280 

Sejvar J., et al. Long-term Neurological and 

Functional Outcome in Nipah virus 

Infection. Ann Neurol. 2007 Sep;62(3): p. 

235–42. 

Seqiris Pty Ltd PV. Q–VAX, Q Fever Vaccine, 

Consumer Medical Information, 2014. 

Sobel, J. Botulism. Clin Infect Dis, 2005. 

41(8): p. 1167–73. 

Smith, D. et al. Alphaviruses. Clinical 

Virology, 3rd ed., ASM Press, 2009. pp. 

1241–1274. 

Spero, L. et al. Staphylococcal enterotoxin A 

(SEA). Methods Enzymol. 1981. 78(Pt A): 

p. 331–6. 

Spickler, A. 2018. Brucellosis. Retrieved from 

http://www.cfsph.iastate.edu/ 

DiseaseInfo/factsheets.php. 

Thapa, M. et al. Conotoxins and their 

regulatory considerations. Reg and Tox 

and Pharm, 2014. 70: p. 197–202. 

Walker, D. Rickettsiae and rickettsial 

infections: the current state of 

knowledge. Clin Infect Dis. 2007. 45 

Suppl 1: p. S39–44. 

Walker, D. Principles of the Malicious Use of 

Infectious Agents to Create Terror— 

Reasons for Concern for Organisms of 

the Genus Rickettsia. Rickettsiology: 

Present and Future Directions, 2003. 990: 

p. 739–742. 

Walton, T., et al., Persistence of neutralizing 

antibody in Equidae vaccinated with 

Venezuelan equine encephalomyelitis 

vaccine strain TC–83. J Am Vet Med 

Assoc., 1972;161(8): p. 916–8. 

Walton, T., et al., Duration of immunity of 

horses vaccinated with strain TC–83 

Venezuelan equine encephalomyelitis 

virus vaccine. Proc Annu Meet U S Anim 

Health Assoc., 1973;77: p. 196–202. 

Weaver, S., et al. Re-emergence of Epidemic 

Venezuelan Equine Encephalomyelitis in 

South America. Lancet, 1996. 348(9025): 

p. 436–40. 

Weaver, S., et al., Genetic determinants of 

Venezuelan equine encephalitis 

emergence. Arch Virol Suppl, 2004. (18): 

p. 43–64. 

World Health Organization, Nipah Virus 

Outbreaks in the WHO South-East Asia 

Region. 2017. Retrieved from 

www.searo.who.int/entity/emerging_

diseases/links/nipah_virus_outbreaks_

sear/en/. 

List of Subjects 

Biologics, Packaging and containers, 

Penalties, Reporting and recordkeeping 

requirements, Transportation. 

For the reasons discussed in the 

preamble, HHS proposes to amend 42 

CFR part 73 as follows: 

PART 73—SELECT AGENTS AND 

TOXINS 

■ 1. The authority citation for part 73 is 

revised to read as follows: 

Authority: 42 U.S.C. 262a; sections 201– 

204, 221 and 231 of Title II of Pub. L. 107– 

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

§ 73.0 [Removed] 

■ 2. Remove § 73.0. 

■ 3. Section 73.1 is amended by: 

■ a. Adding in alphabetical order 

definitions for ‘‘Discovery’’, ‘‘Loss’’, 

‘‘Release’’, and ‘‘Theft’’; 

■ b. Revising the definition of 

‘‘Validated inactivation procedure’’; 

■ c. Adding in alphabetical order 

definitions for ‘‘Validated removal 

procedure’’ and ‘‘Verification viability 

testing protocol’’; and 

■ d. Revising the definition of ‘‘Viability 

testing protocol’’. 

The additions and revision read as 

follows: 

§ 73.1 Definitions. 

* * * * * 

Discovery means the finding of a 

select agent or toxin by an individual or 

entity that is not aware of the select 

agent or toxin’s existence. Examples 

include, but are not limited to, the 

following: 

(1) A registered individual or entity 

finds a select agent or toxin not 

accounted for in their inventory; or 

(2) A non-registered individual or 

entity finds a select agent or toxin. 

* * * * * 

Loss means the inability to account 

for a select agent or toxin known to be 

in the individual or entity’s possession. 

* * * * * 

Release means any of the following: 

(1) An incident resulting in 

occupational exposure to a select agent 

or toxin, 

(2) An incident resulting in animal/ 

plant exposure to a select agent or toxin, 

(3) The failure of equipment used to 

contain a select agent or toxin such that 

it is reasonably anticipated that a select 

agent or toxin was released, 

(4) The failure of or breach in 

personal protective equipment in the 

presence of a select agent or toxin, or 

(5) The failure of biosafety procedures 

such that it is reasonably anticipated 


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that a select agent or toxin was outside 

of containment. 

* * * * * 

Theft means the unauthorized taking 

and removing of a select agent or toxin 

from the possession of an entity or 

individual. 

* * * * * 

Validated inactivation procedure 

means a procedure, whose efficacy has 

been confirmed by data generated from 

an in-house viability testing protocol, to 

render a select agent non-viable but 

allows the select agent to retain 

characteristics of interest for future use; 

or to render any nucleic acids that can 

produce infectious forms of any select 

agent virus non-infectious for future 

use. 

* * * * * 

Validated removal procedure means a 

procedure, whose efficacy has been 

confirmed by data generated in-house 

from a viability testing protocol, to 

confirm removal of all viable select 

agent, or nucleic acids of any select 

agent virus capable of producing 

infectious virus. 

* * * * * 

Verification viability testing protocol 

means a protocol, used on samples that 

have been subjected to a validated 

inactivation or removal procedure, to 

confirm the material is free of all viable 

select agent, or nucleic acids of any 

select agent virus capable of producing 

infectious virus. 

* * * * * 

Viability testing protocol means a 

protocol used to confirm the efficacy of 

the inactivation or removal procedure 

by demonstrating the material is free of 

all viable select agent, or nucleic acids 

of any select agent virus capable of 

producing infectious virus. 

* * * * * 

■ 5. Section 73.2 is revised to read as 

follows: 

§ 73.2 Purpose and scope. 

(a) This part implements the 

provisions of the Public Health Security 

and Bioterrorism Preparedness and 

Response Act of 2002 and the Public 

Health Service Act, 42 U.S.C. 262a, as 

amended, setting forth the requirements 

for possession, use, and transfer of 

select agents and toxins. The biological 

agents and toxins listed in this part have 

the potential to pose a severe threat to 

public health and safety, to animal 

health, or to animal products. Overlap 

select agents and toxins are subject to 

regulation by both CDC and APHIS. 

(b) Any individual or entity in 

possession of a select agent or toxin, for 

which an exclusion or exemption listed 

in this part does not apply, and that is 

not included on a certificate of 

registration issued by the HHS Secretary 

or Administrator for that individual or 

entity, must immediately report such 

possession to either the HHS Secretary 

or Administrator by the submission of 

an APHIS/CDC Form 6. 

■ 6. Section 73.3 is amended by: 

■ a. Revising paragraphs (b), (d)(1), and 

(d)(4) through (6); 

■ b. Redesignating paragraphs (d)(7) 

through (11) as paragraphs as (d)(8) 

through (12), respectively. 

■ c. Adding new paragraph (d)(7); 

■ d. In newly redesignated paragraph 

(d)(8) introductory text, removing the 

text ‘‘100 mg of Conotoxins’’ and adding 

in its place the text ‘‘200 mg of 

Conotoxins’’; 

■ e. In newly redesignated paragraph 

(d)(12) by removing the text ‘‘of the 

conclusion of patient care’’ and adding 

in its place ‘‘from when the individual 

has been released from the medical 

facility where treatment was being 

provided’’; 

■ f. In paragraph (e)(1), removing the 

text ‘‘National Select Agent Registry 

website’’ and adding in its place 

‘‘Federal Select Agent Program 

website’’; 

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

text ‘‘Bacillus cereus Biovar anthracis, 

Botulinum neurotoxins, Botulinum 

neurotoxin producing species of 

Clostridium, Ebola viruses, Francisella 

tularensis, Marburg virus, Variola major 

virus (Smallpox virus), Variola minor 

(Alastrim), or Yersinia pestis’’ and 

adding in its place ‘‘Tier 1 agents and 

toxins’’ and removing the text 

‘‘telephone, facsimile, or email’’ and 

adding in its place the text ‘‘eFSAP 

information system, telephone, or 

email’’; 

■ h. In paragraph (f)(3)(iii), adding the 

text ‘‘not submitted through eFSAP 

information system’’ between the words 

‘‘APHIS/CDC Form 4’’ and ‘‘must’’; and 

■ k. In paragraph (f)(4), adding the text 

‘‘not submitted through eFSAP 

information system’’ between the words 

‘‘form’’ and ‘‘must’’. 

The revisions and additions read as 

follows: 

§ 73.3 HHS select agents and toxins. 

* * * * * 

(b) HHS select agents and toxins: 

Abrin 

Bacillus cereus Biovar anthracis * 

Botulinum neurotoxins * 

Botulinum neurotoxin producing 

species of Clostridium 

Conotoxins (Short, paralytic alpha 

conotoxins containing the following 

amino acid sequence 

X1CCX2PACGX3X4X5X6CX7) 1

Coxiella burnetii 

Crimean-Congo hemorrhagic fever 

virus 2

Diacetoxyscirpenol 

Eastern equine encephalitis virus 2

Ebolavirus * 2

Francisella tularensis * 

Lassa fever virus 2

Lujo virus 2

Marburg virus * 2

Mpox virus (clade I) 2

Reconstructed replication competent 

forms of the 1918 pandemic 

influenza A virus containing any 

portion of the coding regions of all 

eight gene segments (Reconstructed 

1918 influenza A virus) 2

Ricin 

Rickettsia prowazekii 

Severe acute respiratory syndrome 

coronavirus (SARS-CoV) 2

Saxitoxin 

South American hemorrhagic fever 

viruses 2: 

Chapare 

Guanarito 

Junin 

Machupo 

Sabia 

Staphylococcal enterotoxins (subtypes 

A,B,C,D,E) 

T–2 toxin 

Tetrodotoxin 

Tick-borne encephalitis virus 4

Far Eastern subtype 

Siberian subtype 

Kyasanur Forest disease virus 2

Omsk haemorrhagic fever virus 2

Variola major virus (Smallpox virus) * 2

Variola minor virus (Alastrim) * 2

Yersinia pestis * 

1C = Cysteine residues are all present as 

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

the 2nd and 4th Cysteine forming specific 

disulfide bridges; The consensus sequence 

includes known toxins a-MI and a-GI (shown 

above) as well as a-GIA, Ac1.1a, a-CnIA, aCnIB; X1 = any amino acid(s) or Des-X; X2 

= Asparagine or Histidine; P = Proline; A = 

Alanine; G = Glycine; X3 = Arginine or 

Lysine; X4 = Asparagine, Histidine, Lysine, 

Arginine, Tyrosine, Phenylalanine or 

Tryptophan; X5 = Tyrosine, Phenylalanine, 

or Tryptophan; X6 = Serine, Threonine, 

Glutamate, Aspartate, Glutamine, or 

Asparagine; X7 = Any amino acid(s) or Des 

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

have to be present at this position.’’ For 

example, if a peptide sequence were 

XCCHPA then the related peptide CCHPA 

would be designated as Des-X. 2Please refer to https://www.select

agents.gov for current information on 

historical or proposed nomenclature for the 

HHS select agents on the list. 

* * * * * 

(d) * * * 

(1) * * * Except for: 

(i) Any animal which is naturally 

infected with a select agent from its 

natural environment to an artificially 


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5838 Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 

established environment for the purpose 

of the intentional exposure or 

introduction of a select agent to a naı ̈ve 

or experimental animal; or 

(ii) Any animal which is naturally 

infected with a select agent for the 

purpose of the intentional exposure or 

introduction of a select agent to the 

naı ̈ve or experimental animal is placed 

with a naı ̈ve animal in their natural 

environment. 

* * * * * 

(4) A select agent or regulated nucleic 

acids that can produce infectious forms 

of any select agent virus that has been 

subjected to a validated inactivation 

procedure, provided that: 

(i) In-house validation of the 

inactivation procedure is completed 

prior to use; 

(ii) A certificate of inactivation has 

been generated in accordance with 

§ 73.17(a)(8); 

(iii) For use of a select agent surrogate 

to validate an inactivation procedure: 

(A) Select agent surrogates must be 

known to possess equivalent properties 

with respect to inactivation; 

(B) If there are known variations in 

the resistance of a select agent to an 

inactivation procedure, including strain 

to strain, then an inactivation procedure 

must also be validated using the most 

resistant select agent surrogate. 

(iv) For use of a whole tissue or 

homogenized tissue surrogate to 

validate a chemical inactivation 

procedure for other tissues, including 

those in other animal models: 

(A) All standardized conditions must 

be held constant, such as the select 

agent used, tissue volume, and ratio of 

tissue to volume of inactivating 

chemical; 

(B) A safety margin must be 

incorporated into the final chemical 

inactivation procedure to ensure the 

effective inactivation of the select agent; 

(C) The tissue surrogate must meet the 

following criteria: 

(1) The tissue is expected to have the 

highest concentration of the specific 

select agent to be inactivated; or 

(2) The concentration of the select 

agent in the tissue must be determined 

and this select agent concentration must 

not be exceeded when applying the 

validated inactivation procedure on 

subsequent tissue samples. 

(5) Any select agent or regulated 

nucleic acids that can produce 

infectious forms of any select agent 

virus contained in a formalin-fixed 

paraffin-embedded (FFPE) tissue if the 

FFPE process used is a recognized 

procedure for that particular select agent 

or regulated nucleic acids. 

(6) Material containing a select agent 

that is subjected to a validated viable 

select agent removal procedure that has 

rendered the material free of all viable 

select agent provided that: 

(i) In-house validation of the viable 

select agent removal procedure is 

completed prior to use; 

(ii) A certificate of viable select agent 

removal has been generated in 

accordance with § 73.17(a)(8); 

(iii) For use of a surrogate to validate 

a viable select agent removal procedure, 

only surrogates known to possess 

equivalent properties with respect to 

removal are used. 

(A) Select agent surrogates must be 

known to possess equivalent properties 

with respect to inactivation. 

(B) If there are known variations in 

the resistance of a select agent to an 

inactivation procedure, including strain 

to strain, then an inactivation procedure 

must also be validated using the most 

resistant select agent surrogate. 

(iv) A portion of each subsequent 

sample has been subjected to a 

verification viability testing protocol to 

ensure that the validated viable select 

agent removal procedure has rendered 

the material free of all viable select 

agent. 

(7) A select agent or regulated nucleic 

acids that can produce infectious forms 

of any select agent virus not subjected 

to a validated inactivation procedure or 

material containing a select agent not 

subjected to a validated viable select 

agent removal procedure that removes 

all viable select agent cells, spores, or 

virus particles if the material is 

determined by the HHS Secretary to be 

effectively inactivated or effectively 

removed. To apply for a determination, 

an individual or entity must submit a 

written request and supporting 

scientific information to APHIS or CDC. 

A written decision granting or denying 

the request will be issued. 

* * * * * 

■ 7. Section 73.4 is amended by: 

■ a. Revising paragraphs (b), (d)(1), and 

(d)(4) through (6); 

■ b. Redesignating paragraphs (d)(7) 

through (9) as paragraphs (d)(8) through 

(d)(10), respectively. 

■ c. Adding new paragraph (d)(7); 

■ d. In newly redesignated paragraph 

(d)(9), removing the text ‘‘of the 

conclusion of patient care’’ and adding 

in its place ‘‘from when the individual 

has been released from the medical 

facility where treatment was being 

provided’’; 

■ e. Revising newly redesignated 

paragraph (d)(10); 

■ f. In paragraph (e)(1), removing the 

text ‘‘National Select Agent Registry 

website’’ and adding in its place 

‘‘Federal Select Agent Program 

website’’; 

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

text ‘‘Bacillus anthracis, Burkholderia 

mallei and Burkholderia pseudomallei’’ 

and adding in its place ‘‘Tier 1 agents’’ 

and removing the text ‘‘telephone, 

facsimile, or email’’ and adding in its 

place the text ‘‘eFSAP information 

system, telephone, or email’’; 

■ h. In paragraph (f)(3)(iii), adding the 

text ‘‘not submitted through eFSAP 

Information System’’ between the text 

‘‘APHIS/CDC Form 4’’ and ‘‘must’’; 

■ i. In paragraph (f)(4), adding the text 

‘‘not submitted through eFSAP 

information system’’ between the words 

‘‘form’’ and ‘‘must’’. 

The revisions and addition read as 

follows: 

§ 73.4 Overlap select agents and toxins. 

* * * * * 

(b) Overlap select agents and toxins: 

Bacillus anthracis * 

Bacillus anthracis Pasteur strain 

Burkholderia mallei * 

Burkholderia pseudomallei * 

Hendra virus 

Nipah virus * 

Rift Valley fever virus 

Venezuelan equine encephalitis virus 

* * * * * 

(d) * * * 

(1) Except for: 

(i) Any animal which is naturally 

infected with a select agent from its 

natural environment to an artificially 

established environment for the purpose 

of the intentional exposure or 

introduction of a select agent to a naı ̈ve 

or experimental animal; or 

(ii) Any animal which is naturally 

infected with a select agent for the 

purpose of the intentional exposure or 

introduction of a select agent to the 

naı ̈ve or experimental animal is placed 

with a naı ̈ve animal in their natural 

environment. 

* * * * * 

(4) A select agent or regulated nucleic 

acids that can produce infectious forms 

of any select agent virus that has been 

subjected to a validated inactivation 

procedure, provided that: 

(i) In-house validation of the 

inactivation procedure is completed 

prior to use; 

(ii) A certificate of inactivation has 

been generated in accordance with 

§ 73.17(a)(8); 

(iii) For use of a select agent surrogate 

to validate an inactivation procedure: 

(A) Select agent surrogates must be 

known to possess equivalent properties 

with respect to inactivation; 

(B) If there are known variations in 

the resistance of a select agent to an 

inactivation procedure, including strain 

to strain, then an inactivation procedure 


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Federal Register / Vol. 89, No. 20 / Tuesday, January 30, 2024 / Proposed Rules 5839 

must also be validated using the most 

resistant select agent surrogate; 

(iv) For use of a whole tissue or 

homogenized tissue surrogate to 

validate a chemical inactivation 

procedure for other tissues, including 

those in other animal models: 

(A) All standardized conditions must 

be held constant, such as the select 

agent used, tissue volume, and ratio of 

tissue to volume of inactivating 

chemical; 

(B) A safety margin must be 

incorporated into the final chemical 

inactivation procedure to ensure the 

effective inactivation of the select agent; 

(C) The tissue surrogate must meet the 

following criteria: 

(1) The tissue is expected to have the 

highest concentration of the specific 

select agent to be inactivated; or 

(2) The concentration of the select 

agent in the tissue must be determined 

and this select agent concentration must 

not be exceeded when applying the 

validated inactivation procedure on 

subsequent tissue samples. 

(5) Any select agent or regulated 

nucleic acids that can produce 

infectious forms of any select agent 

virus contained in a FFPE tissue if the 

FFPE process used is a recognized 

procedure for that particular select agent 

or regulated nucleic acids. 

(6) Material containing a select agent 

that is subjected to a validated viable 

select agent removal procedure to 

ensure that the validated viable select 

agent removal procedure has rendered 

the material free of all viable select 

agent except for: 

(i) In-house validation of the viable 

select agent removal procedure is 

completed prior to use; 

(ii) A certificate of viable select agent 

removal has been generated in 

accordance with § 73.17(a)(8); 

(iii) For use of a surrogate to validate 

a viable select agent removal procedure, 

only surrogates known to possess 

equivalent properties with respect to 

removal are used; and 

(iv) A portion of each subsequent 

sample has been subjected to a 

verification viability testing protocol to 

ensure that the validated viable select 

agent removal procedure has rendered 

the material free of all viable select 

agent. 

(7) A select agent or regulated nucleic 

acids that can produce infectious forms 

of any select agent virus not subjected 

to a validated inactivation procedure or 

material containing a select agent not 

subjected to a validated viable select 

agent removal procedure that removes 

all viable select agent cells, spores, or 

virus particles if the material is 

determined by the HHS Secretary to be 

effectively inactivated or effectively 

removed. To apply for a determination 

an individual or entity must submit a 

written request and supporting 

scientific information to APHIS or CDC. 

A written decision granting or denying 

the request will be issued. 

* * * * * 

■ 8. Section 73.5 is amended as follows: 

■ a. By revising paragraph (a)(1); 

■ b. In paragraph (a)(3) by removing the 

text ‘‘delivery of patient (i.e., human) 

care by health care professionals has 

concluded’’ and adding in its place ‘‘the 

individual has been released from the 

medical facility where treatment was 

being provided’’. 

■ c. By revising paragraph (a)(4)(i); 

■ d. In paragraph (a)(4)(iv) by adding the 

text ‘‘not submitted through eFSAP 

Information System’’ between the text 

‘‘APHIS/CDC Form 4’’ and ‘‘must’’; 

■ e. In paragraph (b) introductory text 

by removing the article ‘‘a’’ and adding 

in its place the article ‘‘an’’ before 

‘‘HHS’’; 

■ f. By revising paragraph (b)(1); and 

■ g. In the last sentence of paragraph 

(b)(3) by adding the text ‘‘not submitted 

through eFSAP Information System’’ 

between the words ‘‘form’’ and ‘‘must’’. 

The revisions read as follows: 

§ 73.5 Exemptions for HHS select agents 

and toxins. 

(a) * * * 

(1) Unless directed otherwise by the 

HHS Secretary, within seven calendar 

days after identification of the select 

agent or toxin (except for Botulinum 

neurotoxin), or within 30 calendar days 

after identification of Botulinum 

neurotoxin, the select agent or toxin is 

transferred in accordance with § 73.16 

or destroyed on-site by a recognized 

sterilization process or inactivated for 

future use in accordance with section 

73.3 (d)(4). 

* * * * * 

(4) The identification of the agent or 

toxin is reported to CDC or APHIS, the 

specimen provider, and to other 

appropriate authorities when required 

by Federal, State, or local law through 

the eFSAP information system, 

telephone, or email. This report must be 

followed by submission of APHIS/CDC 

Form 4 to APHIS or CDC within seven 

calendar days after identification. 

(i) The identification of HHS Tier 1 

select agents or toxin must be 

immediately reported through the 

eFSAP information system, telephone, 

or email. This report must be followed 

by submission of APHIS/CDC Form 4 

within seven calendar days after 

identification. 

* * * * * 

(b) * * * 

(1) Unless directed otherwise by the 

HHS Secretary, within 90 calendar days 

of receipt, the select agent or toxin is 

transferred in accordance with § 73.16 

or destroyed on-site by a recognized 

sterilization process or inactivated for 

future use in accordance with 

§ 73.3(d)(4). 

* * * * * 

■ 9. Section 73.6 is amended as follows: 

■ a. By revising paragraphs (a) 

introductory text and (a)(1); 

■ b. In paragraph (a)(3) by removing the 

text ‘‘delivery of patient care by health 

care professionals has concluded’’ and 

adding in its place ‘‘the individual has 

been released from the medical facility 

where treatment was being provided’’; 

■ c. By revising paragraph (a)(4)(i); 

■ d. In paragraph (a)(4)(iv) by adding the 

text ‘‘not submitted through eFSAP 

information system’’ between ‘‘APHIS/ 

CDC Form 4’’ and ‘‘must’’; 

■ e. By revising paragraph (b)(1); and 

■ f. In the last sentence of paragraph 

(b)(3) by adding the text ‘‘not submitted 

through eFSAP information system’’ 

between the words ‘‘form’’ and ‘‘must’’. 

The revisions read as follows: 

§ 73.6 Exemptions for overlap select 

agents and toxins. 

(a) Clinical or diagnostic laboratories 

and other entities that possess, use, or 

transfer an overlap select agent or toxin 

that is contained in a specimen 

presented for diagnosis or verification 

will be exempt from the requirements of 

this part for such agent or toxin 

contained in the specimen, provided 

that: 

(1) Unless directed otherwise by the 

HHS Secretary or Administrator, within 

seven calendar days after identification, 

the select agent or toxin is transferred in 

accordance with § 73.16 or 9 CFR 121.16 

or destroyed on-site by a recognized 

sterilization process, or inactivated for 

future use in accordance with 

§ 73.4(d)(4), 

* * * * * 

(4) The identification of the agent or 

toxin is reported to CDC or APHIS, the 

specimen provider, and to other 

appropriate authorities when required 

by Federal, State, or local law through 

the eFSAP information system, 

telephone, or email. This report must be 

followed by submission of APHIS/CDC 

Form 4 to APHIS or CDC within seven 

calendar days after identification. 

(i) The identification of overlap Tier 

1 select agents or toxin must be 

immediately reported through the 

eFSAP information system, telephone, 

or email. This report must be followed 

by submission of APHIS/CDC Form 4 


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within seven calendar days after 

identification. 

* * * * * 

(b) * * * 

(1) Unless directed otherwise by the 

HHS Secretary or Administrator, within 

90 calendar days of receipt, the select 

agent or toxin is transferred in 

accordance with § 73.16 or 9 CFR part 

121.16 or destroyed on-site by a 

recognized sterilization process or 

inactivated for future use in accordance 

with § 73.4 (d)(4), 

* * * * * 

■ 10. Section 73.7 is amended as 

follows: 

■ a. In paragraph (f) by removing ‘‘the 

relevant page(s) of’’ and adding in its 

place ‘‘information related to’’; 

■ b. By revising paragraph (g); 

■ c. In paragraph (i) by removing the 

word ‘‘may’’ and adding in its place the 

word ‘‘must’’ and by removing the word 

‘‘circumstances’’ and adding in its place 

the phrase ‘‘the possession and use of 

the select agents and toxins’’; and 

■ d. In paragraph (i)(1) by removing 

‘‘the relevant page(s) of’’ and adding in 

its place ‘‘information related to’’. 

The revision reads as follows: 

§ 73.7 Registration and related security 

risk assessments. 

* * * * * 

(g) The issuance of a certificate of 

registration may be contingent upon 

inspection and submission of additional 

information to include any or all of the 

following: the security plan, biosafety 

plan, incident response plan, or any 

other information related to the 

requirements of this part. 

* * * * * 

■ 11. Section 73.9 is amended as 

follows: 

■ a. By redesignating paragraphs (a)(5) 

through (9) as paragraphs as (a)(6) 

through (10); 

■ b. By adding new paragraph (a)(5); 

■ c. By revising newly redesignated 

paragraphs (a)(7), (9), and (10); 

■ d. In paragraph (b) by adding a new 

second sentence; 

■ e. By revising paragraph (c)(1); and 

■ f. In the last sentences of paragraphs 

(c)(2) and (d) by adding the phrase ‘‘not 

submitted through eFSAP information 

system’’ between the words ‘‘form’’ and 

‘‘must’’. 

The addition and revision read as 

follows: 

§ 73.9 Responsible Official. 

* * * * * 

(a) * * * 

(5) Not be approved as Responsible 

Official or alternate Responsible Official 

at another registered entity, 

* * * * * 

(7) Ensure that annual inspections are 

conducted for each registered space to 

determine compliance with the 

requirements in accordance with the 

regulations of this part. The results of 

each inspection must be documented, 

and any deficiencies identified during 

an inspection must be corrected and the 

corrections documented. The annual 

inspection must address whether: 

(i) The entity’s biosafety/ 

biocontainment plan is being effectively 

implemented, as outlined in § 73.12. 

(ii) The entity’s security plan is being 

effectively implemented, as outlined in 

§ 73.11. 

(iii) The entity’s incident response 

plan is implemented to ensure whether 

the entity is able to respond, as outlined 

in § 73.14. 

(iv) Each individual with access 

approval from the HHS Secretary or 

Administrator has received the 

appropriate training as outlined in 

§ 73.15. 

* * * * * 

(9) Investigate to determine the reason 

for any failure of a validated 

inactivation or validated viable select 

agent removal procedure to render 

material free from viable select agent. If 

the Responsible Official is unable to 

determine the cause of the failure from 

a validated inactivation or validated 

viable select agent removal procedure or 

receives a report of any inactivation 

failure after the movement of material to 

another location, the Responsible 

Official must report immediately 

through the eFSAP information system, 

telephone or email the inactivation or 

viable select agent removal procedure 

failure to CDC or APHIS. 

(10) Review each of the entity’s 

validated select agent inactivation 

procedure or validated viable select 

agent removal procedure and ensure 

they are revised as necessary. The 

review must be conducted annually or 

after any change in Principal 

Investigator, change in the validated 

inactivation or validated viable select 

agent removal procedure, or failure of 

the validated inactivation or validated 

viable select agent removal procedure. 

The review must be documented, and 

training must be conducted if there are 

any changes to the validated select agent 

inactivation or validated viable select 

agent removal procedure, or viability 

testing protocol. 

(b) * * * An alternate Responsible 

Official can serve at multiple registered 

entities. * * * 

(c) * * * 

(1) The identification of any Tier 1 

agents or toxins must be immediately 

reported through the eFSAP information 

system, telephone, or email. The final 

disposition of the agent or toxin must be 

reported by submission of APHIS/CDC 

Form 4 within seven calendar days after 

identification (except for Botulinum 

neurotoxin and/or Staphylococcal 

enterotoxin (Subtypes A–E)), which is 

within 30 calendar days after 

identification). A copy of the completed 

form not submitted through eFSAP 

information system must be maintained 

for three years. 

* * * * * 

§ 73.10 [Amended] 

■ 12. Section 73.10 is amended in 

paragraph (c) by removing the words ‘‘to 

select agents or toxins’’ and adding in 

their place ‘‘access approval from the 

HHS Secretary or Administrator’’. 

■ 13. Section 73.11 is amended as 

follows: 

■ a. By redesignating paragraphs (c)(9) 

and (10) as paragraphs (c)(10) and (11); 

■ b. By adding a new paragraph (c)(9); 

■ c. In paragraph (d)(4) by removing the 

text ‘‘the area where select agents or 

toxins are used or stored’’ and adding in 

its place ‘‘registered space’’; 

■ d. In paragraph (f) introductory text by 

removing the word ‘‘possessing’’ and 

adding in its place ‘‘registered for’’; 

■ e. In paragraph (f)(1) by removing the 

words ‘‘will have’’ and adding in their 

place ‘‘are registered for’’; 

■ f. By revising paragraph (f)(4)(iii); and 

■ g. By removing paragraph (g) and 

redesignating paragraph (h) as 

paragraph (g). 

The addition and revision read as 

follows: 

§ 73.11 Security. 

* * * * * 

(c) * * * 

(9) Describe procedures to prevent the 

theft, loss, or unauthorized access to a 

select agent or toxin from an effluent 

decontamination system originating 

from a registered laboratory. 

* * * * * 

(f) * * * 

(4) * * * 

(iii) Procedures for screening visitors, 

their property, and, where appropriate, 

vehicles at entry and exit points to 

registered space based on the entity’s 

site-specific risk assessment; 

* * * * * 

■ 14. Section 73.12 is amended as 

follows: 

■ a. In paragraphs (c)(1) and (2) by 

removing the words ‘‘National Select 

Agent Registry website’’ and adding in 

their place ‘‘Federal Select Agent 

Program website’’; 

■ b. By revising paragraph (d); and 

■ c. By adding paragraphs (f), (g), and 

(h). 


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The revision and additions read as 

follows: 

§ 73.12 Biosafety. 

* * * * * 

(d) The biosafety plan must include 

an occupational health plan for 

individuals listed on the individual or 

entity’s registration for access to Tier 1 

select agents and toxins, and those 

individuals must be enrolled in the 

occupational health plan. 

* * * * * 

(f) When an effluent decontamination 

system is used, the plan must provide 

for verification that the liquid waste 

generated from registered space is 

sufficiently treated to prevent the 

release of a select agent or toxin prior 

to discharge of the waste from the 

facility. 

(1) For a new effluent 

decontamination system, verification is 

required before initial use. 

(2) For an effluent decontamination 

system in place, verification is required 

at least once every 12 months and 

following any major change to the 

effluent decontamination system. 

(3) The verification must be 

documented. 

(g) When an effluent decontamination 

system is used, the plan must provide 

that monthly routine maintenance is 

conducted of the effluent 

decontamination system, including at a 

minimum verification that: 

(1) Alarms are functioning according 

to established specifications; 

(2) Piping, pumps, valves, and tanks 

are not leaking; and 

(3) Methods used to monitor and 

record performance measurements and 

are functioning according to established 

specifications. 

(h) An individual or entity must 

document every 12 months the 

following facility verification 

requirements for registered biosafety 

level 3 and animal biosafety level 3 

laboratories. 

(1) Accuracy of devices that monitor 

directional air-flow; 

(2) Confirmation that 

decontamination systems (e.g., 

autoclave, room decontamination 

systems, digesters, liquid effluent 

decontamination systems) are operating 

to ensure the containment of the select 

agent and toxin; 

(3) Confirmation that systems are in 

place to monitor, maintain and validate 

performance of mechanical systems to 

ensure that airflows and differential 

pressures are appropriate to maintain 

containment during normal/operational 

conditions; 

(4) Verification that the facility 

mechanical, electrical, and drain waste 

and ventilation systems responsible for 

containment are inspected, maintained, 

and function as designed manufacturer 

specifications; 

(5) Verification that the facility 

systems perform as intended in 

response to failure conditions as defined 

and tested during commissioning to 

prevent the release of select agent or 

toxin and verify secondary containment: 

(i) Evaluate using work objectives, use 

of space, and facility infrastructure 

systems against the verified original 

design and standards (e.g., Biosafety in 

Microbiological and Biomedical 

Laboratories, NIH Design Requirements 

Manual). 

(ii) Implement controls and alarms to 

identify and alert personnel when 

systems fail, malfunction, or are unable 

to maintain containment during such an 

event. 

(6) Certification of laboratory 

ventilation system HEPA filters, if 

present; 

(7) Confirmation that room integrity 

has been evaluated and repairs are 

addressed (e.g., sealed penetrations); 

(8) Primary containment equipment is 

certified based on manufacturer’s 

specifications (or recommendations) 

(e.g., biological safety cabinets, flexible 

film isolators, animal caging); 

(9) Seals on centrifuges not used in 

primary containment have been checked 

and replaced if needed; and 

(10) Showers, eye wash stations, and 

hands-free sinks are operating properly. 

§ 73.13 [Amended] 

■ 15. Section 73.13 is amended in 

paragraph (a) introductory text by 

adding ‘‘or transfer’’ after ‘‘possess’’. 

■ 16. Section 73.14 is amended as 

follows: 

■ a. In paragraph (b) by adding the 

words ‘‘the failure of an effluent 

decontamination system resulting in a 

release of a select agent or toxin;’’ after 

‘‘a select agent or toxin;’’; 

■ b. By revising paragraph (c); and 

■ c. In paragraph (e) introductory text by 

removing the words ‘‘Entities with’’ and 

adding in their place ‘‘An individual or 

entity registered for’’. 

The revision reads as follows: 

§ 73.14 Incident response. 

* * * * * 

(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 in registered space including any 

animals (including arthropods) or plants 

intentionally or accidentally exposed to 

or infected with a select agent, or an 

effluent decontamination system 

originating from registered space. 

* * * * * 

■ 17. Section 73.15 is amended as 

follows: 

■ a. By adding paragraphs (a)(3) and (4); 

■ b. In paragraph (b) by removing the 

words ‘‘Entities with’’ and adding in 

their place ‘‘An individual or entity 

registered for’’; and 

■ c. By revising paragraph (d). 

The additions and revision read as 

follows: 

§ 73.15 Training. 

* * * * * 

(a) * * * 

(3) Each individual not approved for 

access to HHS and overlap select agents 

and toxins by the HHS Secretary or 

APHIS Administrator whose 

responsibilities routinely place them in 

close proximity (e.g., shared laboratory 

space) to areas where select agents or 

toxins are transferred, possessed, or 

used. The training must be based on the 

particular needs of the individual and 

risks associated with working near areas 

where select agents and toxins are 

handled or stored. The training must 

also instruct each individual on the 

notification requirements related to 

select agents and toxins. Training must 

be accomplished prior to the 

individual’s close proximity to areas 

where select agents or toxins are 

handled or stored and refresher training 

must be provided annually. 

(4) Each individual not approved for 

access to HHS and overlap select agents 

and toxins by the HHS Secretary or 

APHIS Administrator who performs 

administrative or oversight functions of 

the facility related to the transfer, 

possession or use of such agents or 

toxins on behalf of the entity (e.g., 

administrative professionals, facility 

managers, etc.). The training must 

instruct each individual on the 

regulatory requirements relevant to their 

administrative or oversight functions. 

The training must also instruct each 

individual on the notification 

requirements related to select agents 

and toxins. Training must be 

accomplished prior to the individual 

performing these functions and 

refresher training must be provided 

annually. 

(d) The Responsible Official must 

ensure a record of the training provided 

for each individual listed in paragraph 

(a) of this section is maintained. The 

record must include the name of the 

individual who received the training, 

the date of the training, a description of 

the training provided, and the means 

used to verify that the individual 

understood the training. 

* * * * * 


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§ 73.16 Amended] 

■ 18. Section 73.16 is amended in 

paragraph (l) introductory text by 

removing the article ‘‘a’’ and adding in 

its place the article ‘‘an’’ before ‘‘HHS’’. 

■ 19. Section 73.17 is amended as 

follows: 

■ a. By revising paragraphs (a)(1), (2), 

(3), and (8); 

■ d. By removing the last sentence from 

paragraph (c); and 

■ e. By adding paragraph (d). 

The revisions and addition read as 

follows: 

§ 73.17 Records. 

* * * * * 

(a) * * * 

(1) An accurate, current inventory for 

each select agent (including viral 

genetic elements, recombinant and/or 

synthetic nucleic acids, and organisms 

containing recombinant and/or 

synthetic nucleic acids) held in longterm storage (placement in a system 

designed to ensure viability for future 

use, such as in a freezer or lyophilized 

materials), including: 

(i) The name and characteristics (e.g., 

strain designation, GenBank Accession 

number); 

(ii) The quantity acquired from 

another individual or entity (e.g., 

containers, vials, tubes), date of 

acquisition, by whom, and the source; 

(iii) Location where it is stored (e.g., 

building, room number or name, and 

freezer identification or other storage 

container); 

(iv) The date the agent was removed 

and returned, the purpose for using the 

agent, the name of the individual who 

removed and returned the agent, and 

when applicable, date of final 

disposition of the agent and by whom; 

(v) Records created under § 73.16; 

(vi) For intra-entity transfers (sender 

and the recipient are covered by the 

same certificate of registration), name of 

the select agent, the date of the transfer, 

the number of items transferred, the 

name of the sender, and the name of the 

recipient; and 

(vii) Records created under § 73.19. 

(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); 

(3) Accurate, current inventory for 

each toxin held, including: 

(i) The name and characteristics; 

(ii) The quantity acquired from 

another individual or entity (e.g., 

containers, vials, tubes, volume 

including concentration), date of 

acquisition, by whom, and the source; 

(iii) The initial and current amount 

(e.g., milligrams, milliliters, grams); 

(iv) Location where the toxin is stored 

(e.g., building, room number or name, 

and freezer identification or other 

storage container); 

(v) When the toxin was accessed, the 

name of the toxin, the location where 

the toxin was accessed, the date the 

toxin was accessed, the purpose for 

accessing the toxin, the name of the 

individual accessing the toxin, the date 

the toxin was returned back to storage, 

the name of the individual returning the 

toxin back to storage, and date of final 

disposition of the toxin and by whom; 

(vi) Records created under § 73.16; 

(vii) For intra-entity transfers (sender 

and the recipient are covered by the 

same certificate of registration), name of 

the toxin, the date of the transfer, the 

number of vials transferred, the date of 

transfer, the name of the sender, and the 

name of the recipient; and 

(viii) Records created under § 73.19. 

* * * * * 

(8) For select agents or material 

containing select agents or regulated 

nucleic acids that can produce 

infectious forms of any select agent 

virus that have been subjected to a 

validated inactivation procedure or a 

validated viable select agent removal 

procedure: 

(i) A written description of the 

validated inactivation procedure or 

validated viable select agent removal 

procedure used, including validation 

data; 

(ii) A written description of the 

viability testing protocol used; 

(iii) A written description of the 

investigation conducted by the entity’s 

Responsible Official involving a 

validated inactivation or validated 

viable select agent removal failure and 

the corrective actions taken; 

(iv) The name of each individual 

performing the validated select agent 

inactivation or validated viable select 

agent removal; 

(v) The date(s) the validated 

inactivation or validated viable select 

agent removal was completed; 

(vi) The location where the validated 

inactivation or validated viable select 

agent removal was performed; and 

(vii) A signed certificate. The 

certificate must: 

(A) Include the date(s) the validated 

inactivation or validated viable select 

agent removal was completed; 

(B) Include the validated inactivation 

procedure or validated viable select 

agent removal procedure used; 

(C) Include the name of the principal 

investigator; 

(D) Include an attestation statement 

certifying that the information on the 

certificate is true, complete, and 

accurate, and that the validated 

inactivation or validated viable select 

agent removal was performed as 

described in paragraph (a)(8)(i) of this 

section; 

(E) Be signed by the principal 

investigator or designee within 7 days 

after completion of the validated 

inactivation or validated viable select 

agent removal. Such designee must be 

listed on the entity’s registration and 

have the knowledge and expertise to 

provide scientific and technical 

direction regarding the validated 

inactivation procedure or the validated 

viable select agent removal procedure to 

which the certificate refers; 

(F) Be maintained for as long as the 

material is in the possession of the 

registered individual or entity plus an 

additional 3 years; 

(G) A copy of the certificate must 

accompany all transfers of inactivated or 

select agent removed material, including 

intra-entity transfers. 

* * * * * 

(d) All records created in accordance 

with the regulations of this part must be 

maintained for 3 years unless otherwise 

stated. 

§ 73.19 [Amended] 

■ 20. Section 73.19 is amended in 

paragraphs (a)(1) introductory text and 

(b)(1) introductory text by adding 

‘‘eFSAP information system,’’ before the 

word ‘‘telephone’’ and removing the 

word ‘‘email’’ and adding in its place 

‘‘email’’. 

Dated: January 22, 2024. 

Xavier Becerra, 

Secretary, Department of Health and Human 

Services. 

[FR Doc. 2024–01513 Filed 1–26–24; 8:45 am] 

BILLING CODE 4163–18–P 


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