[Federal Register Volume 89, Number 20 (Tuesday, January 30, 2024)]
[Proposed Rules]
[Pages 5823-5842]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-01513]


=======================================================================
-----------------------------------------------------------------------

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:
    <bullet> Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
    <bullet> Mail: Division of Regulatory Science and Compliance, 
Centers for Disease Control and Prevention, 1600 Clifton Road NE, 
Mailstop H21-4,

[[Page 5824]]

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

[[Page 5825]]

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.selectagents.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:
    <bullet> 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.
    <bullet> Loss means the inability to account for a select agent or 
toxin known to be in the individual's or entity's possession.
    <bullet> 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

[[Page 5826]]

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.
    <bullet> Theft means the unauthorized taking and removing of a 
select agent or toxin from the possession of an individual or entity.
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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

[[Page 5827]]

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:
    <bullet> Basic biological safety practices are already sufficient 
to protect laboratory personnel and the public.
    <bullet> Inoculated food samples replicate the concentrations of 
spores that may be naturally found in the foods or soils or sediments.
    <bullet> Botulinum spores are not infectious to the general public 
of healthy individuals older than 1 year of age.
    <bullet> 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

[[Page 5828]]

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:
    <bullet> 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).
    <bullet> 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.
    <bullet> 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.
    <bullet> 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 
X<INF>1</INF>CCX<INF>2</INF>PACGX<INF>3</INF>X<INF>4</INF>X<INF>5</INF>X
<INF>6</INF>CX<INF>7</INF>. 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

[[Page 5829]]

short paralytic alpha-conotoxin and one comment opposed the removal of 
short paralytic alpha-conotoxin. The commenter that opposed removal 
stated that: (1) the LD<INF>50</INF> (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 [mu]g/kg for the short paralytic 
alpha-conotoxin is not a low toxicity compared to other select agents, 
and this LD<INF>50</INF> is actually in line with other marine toxins 
included on the list, such as Tetrodotoxin and Saxitoxin; (2) the 
LD<INF>50</INF> 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 
X<INF>1</INF>CCX<INF>2</INF>PACGX<INF>3</INF>X<INF>4</INF>X<INF>5</INF>X
<INF>6</INF>CX<INF>7</INF>) 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 LD<INF>50</INF> 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 LD<INF>50</INF> 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 Ta[iuml] 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:
    <bullet> Human transmissibility (person-to-person transmission has 
occurred) (Centers for Disease Control and Prevention, 2014; Gurley et 
al., 2007; Luby et al., 2012; and Luby et al., 2009).
    <bullet> High case fatality rate (estimated between 40-100%) (World 
Health Organization, 2017 and Harcourt et al., 2004).
    <bullet> Low infectious dose (ranging from 10\1\-10\7\ plaque 
forming units depending on route of infection) (DeWit et al., 2014; 
Geisbert et al., 2010; and Mathieu et al., 2012).
    <bullet> 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).
    <bullet> 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.

[[Page 5830]]

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.selectagents.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 real-time 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

[[Page 5831]]

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 high-containment 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

[[Page 5832]]

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 
na[iuml]ve or experimental animal; or
    (2) the introduction of a na[iuml]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 na[iuml]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 formalin-fixed 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 agent-free material, to clarify what records are 
needed for inactivated or select agent-free 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 intra-entity transfers. These proposed provisions 
clarify the recordkeeping

[[Page 5833]]

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

[[Page 5834]]

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 wide-ranging 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 foreign-based 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.selectagents.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.

[[Page 5835]]



                                        Estimated Annualized Burden Hours
----------------------------------------------------------------------------------------------------------------
                                                                        Number of     Average burden     Total
            Section                    Form name         Number of    responses per    per response     burden
                                                        respondents    respondent       (in hours)       hours
----------------------------------------------------------------------------------------------------------------
Sections 3 & 4.................  Request for                      1               1                1           1
                                  Exclusions.
Sections 5 & 6.................  Form 4--Report of              917               1                1         917
                                  Identification of a
                                  Select Agent or
                                  Toxin.
Sections 5 & 6.................  Form 5--Request of               1               1                1           1
                                  Exemption.
Section 7......................  Form 1--Application              5               1                5          25
                                  for Registration.
Section 7......................  Form 1 Sec 6A--                144               5                1         720
                                  Amendment to a
                                  Certificate of
                                  Registration.
Section 9......................  Documentation of self-         233               1                1         233
                                  inspection.
Section 10.....................  Request for Expedited            1               1            30/60           1
                                  Review.
Section 11.....................  Security Plan........          233               1                1         233
Section 12.....................  Biosafety Plan.......          233               1                1         233
Section 13.....................  Request Regarding a              3               1                2           6
                                  Restricted
                                  Experiment.
Section 14.....................  Incident Response              233               1                1         233
                                  Plan.
Section 15.....................  Training.............          233             1.5              1.5       339.5
Section 16.....................  Form 2--Request to             229               1              1.5         380
                                  Transfer Select
                                  Agents and Toxins.
Section 17.....................  Records..............          233               1            30/60         117
Section 19.....................  Form 3--Notification           185               1                1         185
                                  of Theft, Loss, or
                                  Release.
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/annual-cases.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-BiosafetyMicrobiologicalBiomedicalLaboratories-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.

[[Page 5836]]

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 Fever-Rickettsia 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 Squirrel-Associated 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

0
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).


Sec.  73.0  [Removed]

0
2. Remove Sec.  73.0.
0
3. Section 73.1 is amended by:
0
a. Adding in alphabetical order definitions for ``Discovery'', 
``Loss'', ``Release'', and ``Theft'';
0
b. Revising the definition of ``Validated inactivation procedure'';
0
c. Adding in alphabetical order definitions for ``Validated removal 
procedure'' and ``Verification viability testing protocol''; and
0
d. Revising the definition of ``Viability testing protocol''.
    The additions and revision read as follows:


Sec.  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

[[Page 5837]]

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.
* * * * *
0
5. Section 73.2 is revised to read as follows:


Sec.  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.
0
6. Section 73.3 is amended by:
0
a. Revising paragraphs (b), (d)(1), and (d)(4) through (6);
0
b. Redesignating paragraphs (d)(7) through (11) as paragraphs as (d)(8) 
through (12), respectively.
0
c. Adding new paragraph (d)(7);
0
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'';
0
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'';
0
f. In paragraph (e)(1), removing the text ``National Select Agent 
Registry website'' and adding in its place ``Federal Select Agent 
Program website'';
0
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'';
0
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
0
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:


Sec.  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 
X<INF>1</INF>CCX<INF>2</INF>PACGX<INF>3</INF>X<INF>4</INF>X<INF>5</INF>X
<INF>6</INF>CX<INF>7</INF>) \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 *

    \1\ C = Cysteine residues are all present as disulfides, with 
the 1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming 
specific disulfide bridges; The consensus sequence includes known 
toxins a-MI and a-GI (shown above) as well as a-GIA, Ac1.1a, a-CnIA, 
a-CnIB; X1 = any amino acid(s) or Des-X; X2 = Asparagine or 
Histidine; P = Proline; A = Alanine; G = Glycine; X3 = Arginine or 
Lysine; X4 = Asparagine, Histidine, Lysine, Arginine, Tyrosine, 
Phenylalanine or Tryptophan; X5 = Tyrosine, Phenylalanine, or 
Tryptophan; X6 = Serine, Threonine, Glutamate, Aspartate, Glutamine, 
or Asparagine; X7 = Any amino acid(s) or Des X and; ``Des X'' = ``an 
amino acid does not have to be present at this position.'' For 
example, if a peptide sequence were XCCHPA then the related peptide 
CCHPA would be designated as Des-X.
    \2\ Please refer to https://www.selectagents.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

[[Page 5838]]

established environment for the purpose of the intentional exposure or 
introduction of a select agent to a na[iuml]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 na[iuml]ve or experimental animal is placed with a 
na[iuml]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 Sec.  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 Sec.  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.
* * * * *
0
7. Section 73.4 is amended by:
0
a. Revising paragraphs (b), (d)(1), and (d)(4) through (6);
0
b. Redesignating paragraphs (d)(7) through (9) as paragraphs (d)(8) 
through (d)(10), respectively.
0
c. Adding new paragraph (d)(7);
0
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'';
0
e. Revising newly redesignated paragraph (d)(10);
0
f. In paragraph (e)(1), removing the text ``National Select Agent 
Registry website'' and adding in its place ``Federal Select Agent 
Program website'';
0
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'';
0
h. In paragraph (f)(3)(iii), adding the text ``not submitted through 
eFSAP Information System'' between the text ``APHIS/CDC Form 4'' and 
``must'';
0
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:


Sec.  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 na[iuml]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 na[iuml]ve or experimental animal is placed with a 
na[iuml]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 Sec.  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

[[Page 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 Sec.  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.
* * * * *
0
8. Section 73.5 is amended as follows:
0
a. By revising paragraph (a)(1);
0
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''.
0
c. By revising paragraph (a)(4)(i);
0
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'';
0
e. In paragraph (b) introductory text by removing the article ``a'' and 
adding in its place the article ``an'' before ``HHS'';
0
f. By revising paragraph (b)(1); and
0
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:


Sec.  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 Sec.  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 Sec.  73.16 or destroyed on-site by a recognized 
sterilization process or inactivated for future use in accordance with 
Sec.  73.3(d)(4).
* * * * *
0
9. Section 73.6 is amended as follows:
0
a. By revising paragraphs (a) introductory text and (a)(1);
0
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'';
0
c. By revising paragraph (a)(4)(i);
0
d. In paragraph (a)(4)(iv) by adding the text ``not submitted through 
eFSAP information system'' between ``APHIS/CDC Form 4'' and ``must'';
0
e. By revising paragraph (b)(1); and
0
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:


Sec.  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 Sec.  73.16 or 
9 CFR 121.16 or destroyed on-site by a recognized sterilization 
process, or inactivated for future use in accordance with Sec.  
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

[[Page 5840]]

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 Sec.  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 Sec.  73.4 (d)(4),
* * * * *
0
10. Section 73.7 is amended as follows:
0
a. In paragraph (f) by removing ``the relevant page(s) of'' and adding 
in its place ``information related to'';
0
b. By revising paragraph (g);
0
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
0
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:


Sec.  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.
* * * * *
0
11. Section 73.9 is amended as follows:
0
a. By redesignating paragraphs (a)(5) through (9) as paragraphs as 
(a)(6) through (10);
0
b. By adding new paragraph (a)(5);
0
c. By revising newly redesignated paragraphs (a)(7), (9), and (10);
0
d. In paragraph (b) by adding a new second sentence;
0
e. By revising paragraph (c)(1); and
0
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:


Sec.  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 Sec.  73.12.
    (ii) The entity's security plan is being effectively implemented, 
as outlined in Sec.  73.11.
    (iii) The entity's incident response plan is implemented to ensure 
whether the entity is able to respond, as outlined in Sec.  73.14.
    (iv) Each individual with access approval from the HHS Secretary or 
Administrator has received the appropriate training as outlined in 
Sec.  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.
* * * * *


Sec.  73.10  [Amended]

0
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''.
0
13. Section 73.11 is amended as follows:
0
a. By redesignating paragraphs (c)(9) and (10) as paragraphs (c)(10) 
and (11);
0
b. By adding a new paragraph (c)(9);
0
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'';
0
d. In paragraph (f) introductory text by removing the word 
``possessing'' and adding in its place ``registered for'';
0
e. In paragraph (f)(1) by removing the words ``will have'' and adding 
in their place ``are registered for'';
0
f. By revising paragraph (f)(4)(iii); and
0
g. By removing paragraph (g) and redesignating paragraph (h) as 
paragraph (g).
    The addition and revision read as follows:


Sec.  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;
* * * * *
0
14. Section 73.12 is amended as follows:
0
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'';
0
b. By revising paragraph (d); and
0
c. By adding paragraphs (f), (g), and (h).

[[Page 5841]]

    The revision and additions read as follows:


Sec.  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.


Sec.  73.13  [Amended]

0
15. Section 73.13 is amended in paragraph (a) introductory text by 
adding ``or transfer'' after ``possess''.
0
16. Section 73.14 is amended as follows:
0
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;'';
0
b. By revising paragraph (c); and
0
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:


Sec.  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.
* * * * *
0
17. Section 73.15 is amended as follows:
0
a. By adding paragraphs (a)(3) and (4);
0
b. In paragraph (b) by removing the words ``Entities with'' and adding 
in their place ``An individual or entity registered for''; and
0
c. By revising paragraph (d).
    The additions and revision read as follows:


Sec.  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.
* * * * *

[[Page 5842]]

Sec.  73.16  Amended]

0
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''.
0
19. Section 73.17 is amended as follows:
0
a. By revising paragraphs (a)(1), (2), (3), and (8);
0
d. By removing the last sentence from paragraph (c); and
0
e. By adding paragraph (d).
    The revisions and addition read as follows:


Sec.  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 long-term 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 Sec.  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 Sec.  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 Sec.  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 Sec.  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.


Sec.  73.19  [Amended]

0
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