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Rule2024-29583

Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins

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Published

December 17, 2024

Effective

January 16, 2025

Issuing agencies

Health and Human Services Department

Abstract

This rule finalizes updates to the HHS list of select agents and toxins that could pose a severe threat to public health and safety. These updates were proposed along with other changes to the select agent and toxin regulations, which will be addressed in a separate regulatory action. In a companion document published in this issue of the Federal Register, the U.S. Department of Agriculture (USDA) is making parallel regulatory changes.

Full Text

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<title>Federal Register, Volume 89 Issue 242 (Tuesday, December 17, 2024)</title>
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[Federal Register Volume 89, Number 242 (Tuesday, December 17, 2024)]
[Rules and Regulations]
[Pages 101941-101952]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-29583]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 73

[Docket No. CDC-2020-0024]
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: Final rule.

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SUMMARY: This rule finalizes updates to the HHS list of select agents
and toxins that could pose a severe threat to public health and safety.
These updates were proposed along with other changes to the select
agent and toxin regulations, which will be addressed in a separate
regulatory action. In a companion document published in this issue of
the Federal Register, the U.S. Department of Agriculture (USDA) is
making parallel regulatory changes.

DATES: This final rule is effective January 16, 2025.

FOR FURTHER INFORMATION CONTACT: Daniel A. Singer, MD, Acting Director,
Division of Regulatory Science and Compliance, Centers for Disease
Control and Prevention, 1600 Clifton Road NE, Mailstop H21-4, Atlanta,
Georgia 30329. Telephone: (404) 553-8266.

SUPPLEMENTARY INFORMATION: The final rule is organized as follows:

I. Background
A. Legal Authority
B. 2024 Proposed Rule
II. Responses to Comments and Provisions of the Proposed Rule
A. Removal of Brucella abortus, Brucella melitensis, and
Brucella suis
B. Nomenclature and Other Changes in the Select Agent and Toxin
List
C. Additional Comments Received
D. Retaining Tier 1 Designation of Botulinum Neurotoxin
Producing Species of Clostridium
E. No Addition of Hantaviruses
F. Toxin Review: Changes to Exclusion Limits for Short,
Paralytic Alpha Conotoxins
G. Designation of Nipah Virus as a Tier 1 Select Agent
H. Addition of a Footnote to the HHS Select Agent and Overlap
Select Agent List
I. Summary of Final Rule Provisions
III. Alternatives Considered
IV. Required Regulatory Analyses
A. Executive Orders 12866, 13563, and 14094
B. The Regulatory Flexibility Act (RFA), as Amended by the Small
Business Regulatory Enforcement Fairness Act (SBREFA)

[[Page 101942]]

C. Paperwork Reduction Act of 1995
D. E.O. 12988: Civil Justice Reform
E. E.O. 13132: Federalism
F. Plain Language Act of 2010
V. References

I. Background

A. Legal Authority

Under the Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (Bioterrorism Response Act), the HHS Secretary
must, by regulation, establish and maintain 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:
<bullet> the effect on human health of exposure to an agent or
toxin;
<bullet> the degree of contagiousness of the agent and the methods
by which the agent or toxin is transferred to humans;
<bullet> the availability and effectiveness of pharmacotherapies
and immunizations to treat and prevent illnesses resulting from an
agent or toxin; and
<bullet> any other criteria, including the needs of children and
other vulnerable populations, that the HHS Secretary considers
appropriate (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.
In the preparation of this rulemaking, HHS/CDC considered the
statutory criteria and evaluated each agent and toxin based on the
following:
<bullet> Effect on human health:
[cir] the degree of pathogenicity (ability of an organism to cause
disease);
[cir] long-term health effects;
[cir] severity of illness;
[cir] case fatality rate;
[cir] status of host immunity (e.g., whether an individual has
already been exposed to the agent and generated an immune response);
[cir] vulnerability of special populations;
<bullet> Degree of contagiousness:
[cir] dissemination efficacy;
[cir] aerosol stability;
[cir] rate of transmission;
<bullet> Availability and effectiveness of pharmacotherapies:
[cir] available treatment;
<bullet> Other Criteria:
[cir] decontamination and restoration (the extent remediation
efforts are needed due to agent persistence in the environment and
population);
[cir] matrix stability;
[cir] ease of production;
[cir] ability to genetically manipulate or alter;
[cir] the burden or impact on the health care system.
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. These two agencies administer the HHS and
USDA select agent and toxin regulations and coordinate Federal
oversight of select agents and toxins in a manner to minimize the
administrative burden on the regulated community.
The list of HHS select agents and toxins is divided into two
sections--agents and toxins regulated solely by HHS and agents that are
regulated by both HHS and USDA. 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 Sec. 73.4 (overlap select
agents and toxins) have the potential to pose a severe threat to human
health and safety, as determined by HHS, and a severe threat to animals
and animal products, as determined by the USDA, pursuant to USDA's
authority under the Agriculture Bioterrorism Protection Act of 2002 (7
U.S.C. 8401). 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). 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.

B. 2024 Proposed Rule

On March 17, 2020, CDC published an advance notice of proposed
rulemaking (ANPRM) (85 FR 15087) seeking public comments on potential
changes to the current list of HHS and overlap select agents and toxins
that are regulated by both HHS and USDA. The received comments broadly
supported removal of the Brucella species--of the 335 comments
received, 325 supported removal of one or more species of Brucella.
Only two commenters were in favor of retaining the Brucella species.
HHS/CDC engaged the Intragovernmental Select Agents and Toxins
Technical Advisory Committee (ISATTAC) to review and consider the
public comments. The committee reviewed the public comments over a
series of seven meetings held between June 12, 2020, and December 11,
2020. Other Federal subject-matter experts were invited to the meetings
to address questions from the committee. The ANPRM also requested input
on removal of other agents from the list (e.g., Coxiella burnetii,
Rickettsia prowazekii, Bacillus anthracis [Pasteur strain]). After
considering public comments, ISATTAC advisory input, and Federal
subject-matter experts' input, CDC proposed changes to the select agent
and toxin list and removal of three species of Brucella.
On January 30, 2024, HHS issued a proposed rule entitled
``Possession, Use, and Transfer of Select Agents and Toxins; Biennial
Review of the List of Select Agents and Toxins'' (89 FR 5823). The
proposed rule included two sets of proposals: (1) regulatory changes
related to the select agents and toxins on the list (i.e., remove three
species of Brucella from the list of overlap select agents and toxins,
raise one toxin's exclusion amounts, rename three viruses, designate a
current agent as a Tier 1 agent, and remove the designation of Tier 1
status from one agent), and (2) regulatory changes related to the
administration of FSAP. This second set of proposals included adding
definitions and provisions to clarify inactivation of select agents,
adding requirements to report discoveries of select agents and toxins,
and codifying policies regarding effluent decontamination systems and
biosafety provisions for facility verification requirements for
registered biosafety level 3 and animal biosafety level 3 laboratories.
HHS/CDC has elected to finalize the January 30, 2024, proposed rule
in two separate rulemakings--one final rule focused on changes to the
select agents and toxins list (this final rule), and a second final
rule focused on regulatory changes to the administration of the FSAP
discussed above. This final rule will focus solely on removing three
select agents, raising one toxin's exclusion limit, updating
nomenclature, and designating an agent as Tier 1. HHS/CDC is proceeding
with two final rules for clarity and to avoid any unnecessary delay in
finalizing the revised select agents and toxins list. HHS/CDC will
publish another regulatory action focused on the proposed rule's
administrative and programmatic changes at a later date. Like HHS/CDC,
USDA/APHIS is also

[[Page 101943]]

proceeding with two separate final rules for this rulemaking.
Interested persons or organizations were invited to participate by
submitting written views, recommendations, and data. HHS/CDC invited
general comments 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 and
immunizations to treat and prevent any illness resulting from infection
by the agent or toxin;'' and
(4) ``any other criteria, including the needs of children and other
vulnerable populations, that the Secretary considers appropriate''.
Comments were also requested on the following specific proposed
changes to the list of HHS select agents and toxins:
<bullet> Removal of Brucella abortus, Brucella melitensis, and
Brucella suis: Proposal to remove Brucella abortus, Brucella
melitensis, and Brucella suis from the select agent list.
<bullet> Updates to nomenclature of select agents: To change ``SARS
coronavirus (SARS-CoV)'' to ``Severe acute respiratory syndrome
coronavirus (SARS-CoV)'' to correct the nomenclature; to remove the
exclusion regarding South American genotype of Eastern Equine
Encephalitis virus as this terminology is no longer the correct
nomenclature; and to rename Ebola virus to Ebolavirus in accordance
with the recent taxonomic change by the International Committee on
Taxonomy of Viruses (ICTV) (this was initially included as its own
section in the proposed rule but moved under this section for
nomenclature changes).
<bullet> Updates to nomenclature of monkeypox virus: Proposal to
update the terminology of ``monkeypox virus,'' which was initially
proposed to be updated to ``Mpox Clade I.''
<bullet> Removal of the Designation of Botulinum neurotoxin
producing species of Clostridium as a Tier 1 Agent: Proposal to retain
botulinum neurotoxin producing species of Clostridium as an HHS select
agent, but no longer list it as a Tier 1 agent.
<bullet> No Addition of Hantaviruses: Proposal to not add Sin
Nombre virus (SNV), Andes virus (ANDV), Hantaan virus (HTNV), and
Dobrava virus (DOBV) to the select agent list.
<bullet> Toxin Review: Changes to Exclusion Limits for Short,
Paralytic Alpha Conotoxins: Proposal to increase the exclusion amount
for short, paralytic alpha conotoxins from 100 mg to 200 mg.
<bullet> Designation of Nipah virus as a Tier 1 Select Agent:
Proposal to designate Nipah virus as a Tier 1 select agent.
<bullet> Addition of a Footnote to the HHS Select Agent List on the
FSAP website: Proposal to add a footnote to the list for HHS and
Overlap select agents indicating that the current nomenclature will be
available on the FSAP website (<a href="https://www.selectagents.gov">https://www.selectagents.gov</a>) to
harmonize the list of select agent viruses with ICTV nomenclature.
The public comment period for the proposed rule ended on April 1,
2024. HHS/CDC received 44 unique comments from individuals,
stakeholders, and groups and carefully reviewed and considered the
comments in this preparation of the final rule. Of these 44 comments,
37 include discussion of the list of select agents discussed in this
final rule. A summary of the comments relevant to the content of this
final rule and responses to those comments are found at section II,
below. Public comments addressing other topics from the proposed rule
will be addressed in a separate regulatory action.

II. Responses to Comments and Provisions of the Proposed Rule

The following is a section-by-section discussion of the changes
HHS/CDC is making to the list of select agents and toxins in 42 CFR
73.3 and 73.4 after consideration of public comments. As previously
stated, the changes proposed in the proposed rule will be finalized in
two separate rules. This final rule addresses changes to the list of
select agents and toxins in 42 CFR 73.3 and 73.4. All other revisions
to definitions, policies, and regulatory requirements addressed in the
proposed rule will be addressed in a separate final rule.

A. Removal of Brucella abortus, Brucella melitensis, and Brucella suis

Regarding the request for comment on whether to remove three
species of Brucella (B. abortus, B. melitensis, and B. suis) from the
select agent and toxins list, HHS/CDC received 37 comments from
individuals, animal health groups, regulated entities, and public
health associations that fully supported removing the three agents. No
public comments proposed maintaining these agents on the select agent
and toxins list.
Individuals and animal health groups stated that they support
removing B. abortus, B. melitensis, and B. suis to allow for more
robust studies on alternative methods of surveillance, effective
delivery mechanisms for wildlife vaccination, and techniques to limit
disease spread, such as contraception and novel sustained-release
antibiotics in conjunction with immuno-contraception. Commenters stated
the etiology and pathophysiology of the Brucella species make it poorly
suited to cause a severe threat to human health. Commenters further
noted that the disease is extremely rare in North America and has
limited capacity for human-to-human transmission. The same commenters
stated maintaining the Brucella species as select agents causes
considerable burden to the research community, impairing necessary
scientific developments of diagnostic tools and vaccine delivery
methods. Regulatory constraints on Brucella species were further
correlated to fewer individuals entering the field of Brucella
research. The commenters agreed removal of these agents would not
affect the nationally recognized biosafety measures used by U.S.
researchers in handling these agents. Commenters also noted that,
regardless of the FSAP's regulation of these agents, Brucella species
remain endemic worldwide. This change would, however, enhance proactive
measures for research and diagnostics.
State veterinarians, state agriculture departments, and livestock
associations also support the removal of the Brucella species and
believe delisting these agents will allow for faster production of
improved diagnostics. These groups believe delisting ultimately will
reduce the cost for ranching families and other taxpayers when
performing the required testing on domestic livestock. These groups
stated that current tests often cross-react or result in false
positives that threaten animal agribusinesses; the benefits to delist
the Brucella species are numerous; and the perceived risk to national
security is not supported by peer-reviewed science. One group stated
removal of these agents is a step toward using a modernized risk-based
approach for biosafety and security.
Regulated entities (i.e., entities registered with FSAP under 42
CFR 73.7) reported similar support for removing B. abortus, B.
melitensis, and B. suis and included that they have no concerns with
maintaining work using BSL-3/ABSL-3 practices. Commenters stated that
guidance will be needed for the regulated community currently
registered for these agents on how to remove registered space and/or
removal of Brucella species from registration while active work is
ongoing with Brucella.

[[Page 101944]]

Public health associations commented that B. abortus, B.
melitensis, and B. suis should be removed because of the low mortality
rate and because current molecular and diagnostic methods allow for the
effective detection of the agents. Comments stated delisting these
agents will remove substantial regulatory requirements on individuals,
specifically the Responsible Official and Alternate Responsible
Official, and allow for an expanded work staff to contribute to
testing. Further, antibiotic treatment regimens are effective and well-
established for treating brucellosis due to infections with B. abortus,
B. melitensis, or B. suis.
In accordance with the proposed rule and public comments, HHS/CDC
is removing B. abortus, B. melitensis, and B. suis from the select
agent and toxins list upon publication of the final rule. This decision
is based on the criteria and considerations outlined in 42 U.S.C. 262a,
including the low mortality rate, rare human-to-human transmission, and
availability of therapeutics, and is supported by the strong and
unanimous support received through public comments in favor of removing
these agents (Olsen et al., 2018). Please note that all entities
currently working with B. abortus, B. melitensis, or B. suis will need
to remove these agents from their APHIS/CDC Form 1 (registration),
including Sections 3, 7A/C (and associated attachments), and 7B. FSAP
will be reaching out to affected entities upon publication of this
final rule. Further guidance can be found at <a href="https://www.selectagents.gov/efsap/using/form1/docs/eFSAP_Form_1_Amendments_Guidance_508.pdf">https://www.selectagents.gov/efsap/using/form1/docs/eFSAP_Form_1_Amendments_Guidance_508.pdf</a>.
For brucellosis case reporting and national notification, please
visit <a href="https://www.cdc.gov/brucellosis/hcp/surveillance/index.html">https://www.cdc.gov/brucellosis/hcp/surveillance/index.html</a>.
Additionally, BSL-3/ABSL-3 laboratory safety and containment
recommendations for Brucella species are outlined in the Biosafety in
Microbiological and Biomedical Laboratories (BMBL) found at <a href="https://www.cdc.gov/labs/bmbl/index.html">https://www.cdc.gov/labs/bmbl/index.html</a>.

B. Nomenclature and Other Changes in the Select Agent and Toxin List

HHS/CDC proposed to amend the select agent list by updating
``monkeypox virus'' to the regulated virus variant ``Mpox virus (clade
I).'' Initially, HHS/CDC based this change on the World Health
Organization (WHO) recommendation to adopt a new disease name from
monkeypox to mpox (<a href="https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease">https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease</a>). This was updated in the
International Classification of Diseases (ICD) system (<a href="https://icd.who.int/browse/2024-01/mms/en#160886685">https://icd.who.int/browse/2024-01/mms/en#160886685</a>).
Global experts, including the International Committee on the
Taxonomy of Viruses, assigned new names to the monkeypox virus variants
but not to the virus itself. The virus variants became known as
monkeypox virus Clade I (formerly Congo Basin, Central African clade)
and Clade II (formerly West African Clade) (<a href="https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new-names">https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new-names</a>).
These efforts were in part to align the disease name and virus variants
with current best naming practices.
FSAP issued guidance during the 2022 mpox outbreak to assist
individuals and entities to comply with select agent and toxin
regulations after they identified monkeypox virus in diagnostic
samples. The guidance clarified that when materials are identified as
being or containing monkeypox virus, and the clade is unknown, the
materials are considered select agents. The guidance also explained
when regulatory exemptions and exclusions would apply. This guidance
was issued based on current diagnostic assays not being specific to the
monkeypox virus clade.
Based on these considerations and recognition that this change
would have implications beyond a change in nomenclature, HHS/CDC will
not change the listed agent from ``monkeypox virus'' to ``Mpox virus
(clade I).'' The decision to retain the existing listing is to ensure
consistency in nomenclature and the regulation of select agent
material. FSAP does not include clade-specific designations for other
select agents, but the regulations provide exclusions when appropriate.
This ensures select agent material is possessed, used, and transferred
in accordance with the regulations, which is critically important when
clade-specific assays are generally used. Therefore, HHS/CDC is
retaining the current listing and monkeypox virus, meaning monkeypox
virus with clade unknown is a select agent. Likewise, monkeypox virus
identified as clade I is a select agent. The decision to retain the
current listing means no changes are made to the regulation of this
select agent or the applicable exclusions and exemptions.
As mentioned above, monkeypox virus contains two virus variants, or
clades. In 2012, HHS/CDC excluded the West African Clade of monkeypox
virus from the select agent regulatory requirements (<a href="https://www.selectagents.gov/sat/exclusions/hhs.htm">https://www.selectagents.gov/sat/exclusions/hhs.htm</a>). Excluded select agents
have been determined to not pose a severe threat to public health and
safety and are not regulated as select agents. Though not explicitly
proposed in the proposed rule, HHS/CDC has decided to rename the
excluded West African Clade monkeypox virus to clade II monkeypox
virus. This nomenclature change aligns with WHO recommendations (Ulaeto
et al., 2023, <a href="https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease">https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease</a>). This change promotes consistent
terminology in global and public health and will not impact regulated
entities.
Additionally, HHS/CDC proposed to change SARS coronavirus (SARS-
CoV) to ``Severe acute respiratory syndrome coronavirus (SARS-CoV),''
which is the correct nomenclature. This nomenclature change was also
supported by two comments and is finalized as proposed.
Though ``Eastern equine encephalitis virus'' is an HHS select
agent, the regulations exclude any South American genotype of Eastern
Equine Encephalitis Virus from the requirements. HHS/CDC proposed to
remove the exclusion regarding South American genotype of Eastern
Equine Encephalitis virus as this no longer reflected the appropriate
nomenclature, but did not provide the updated virus name. The updated
nomenclature of the South American genotype of Eastern Equine
Encephalitis virus is ``Madariaga virus.'' HHS/CDC received two
comments requesting clarification on whether Madariaga virus would be
excluded from regulatory requirements and one comment in favor of this
exclusion. The nomenclature of the excluded South American genotype of
Eastern Equine Encephalitis virus is finalized as ``Madariaga virus.''
For clarity, 42 CFR 73.3(d)(12) will now read as excluding ``Madariaga
virus'' from the regulatory requirements.
Lastly, HHS/CDC proposed the renaming of Ebola virus to the genus
Ebolavirus. HHS/CDC received 10 public comments that supported renaming
Ebola virus to the genus Ebolavirus to align with the International
Committee on Taxonomy of Viruses (ICTV). None of the commenters
provided evidence or rationale for their support of this change. One
commenter stated that HHS/CDC should also make it clear that any strain
that is similar enough to this genus, whether naturally discovered or
artificially derived, should be regarded as a select agent. HHS/CDC
will not make any changes based on this comment but does note that any
virus

[[Page 101945]]

(including separate strains or species) that is classified as being a
member of the genus Ebolavirus would be subject to the requirements of
this part. The renaming of Ebolavirus is finalized as proposed.

C. Additional Comments Received

HHS/CDC also received three public comments recommending the
removal of monkeypox virus (clade I) from the HHS list of select agents
and toxins. One commenter stated that given the virulence and
transmission patterns of circulating strains of clade I combined with
the similarity of prophylaxis and treatment measures for both clade I
and II, they did not feel it should be regarded as a select agent any
longer. Another commenter stated that the risk of a severe monkeypox
virus (clade I) outbreak in the United States is likely minimal, given
the low risk of casual human-to-human transmission; mild clinical
symptoms for immunocompetent people; low mortality rate; an FDA-
approved, effective vaccine; availability of pharmacotherapy treatment;
and a robust healthcare infrastructure and public health response. The
final commenter recommended removal of monkeypox virus (clade I), as
its status as a select agent could potentially restrict early detection
via wastewater surveillance and may lead to unnecessary burdens on
healthcare facilities, particularly in under-resourced communities.
This commenter stated that removing monkeypox virus (clade I) from the
select agent list would remove barriers to rapid diagnosis, ensure
equitable access to care, and streamline public health response efforts
by increasing accessibility to testing in the event monkeypox virus
(clade I) begins to circulate in the United States. The select agent
regulations include provisions that exempt diagnostic laboratories from
the requirements, as long as these laboratories secure, destroy, and
report positive samples. This exemption allows for continued rapid
diagnosis, equitable access to care, and a robust public health
response effort. As new data from current outbreaks are collected and
analyzed, HHS/CDC will take these comments along with future data into
consideration during the next biennial review. The review process
considers how the agent affects human health, the degree of
transmissibility, if there are effective medical countermeasures
available, and the needs of vulnerable populations. Appropriate
departments and agencies with scientific experts will also be
consulted. At present, more data would be needed to support the removal
of monkeypox virus from the select agent list, so monkeypox virus will
remain on the list as an HHS-only select agent, and monkeypox virus
(clade I) will remain a regulated variant.
Additionally, one commenter stated that they do not support the
addition of SARS-CoV/SARS-CoV-2 chimeric viruses, which were previously
added as a select agent on November 17, 2021. HHS/CDC is not making
changes to the final rule based on this comment. A final rule published
on March 3, 2023 (88 FR 13322), outlines the basis for adding SARS-CoV/
SARS-CoV-2 chimeric viruses resulting from any deliberate manipulation
of SARS-CoV-2 to incorporate nucleic acids coding for SARS-CoV
virulence factors as an HHS select agent.
One commenter inquired why H2N2 (a subtype of Influenza A virus)
was not considered a select agent, especially since NIAID's Laboratory
of Infectious Diseases published that the 1957 pandemic strain of H2N2
would most likely cause a pandemic. As mentioned above, changes to the
list of select agents and toxins are carefully considered using
specific criteria and in consultation with appropriate departments,
agencies, and scientific experts. This review also takes into account
current data to support changes to the list. FSAP will continue
assessing changes to the select agent and toxin list as part of its
ongoing biennial review process, but HHS/CDC is not making any changes
based on this comment at this time.
Another commenter stated that, given the further development of
reverse genetics systems, FSAP should consider oversight of the nucleic
acids, in part or in whole, that could be used to create select agents.
HHS/CDC is not making any changes based on this comment but does
understand that the ability to synthetically create agents capable of
posing a severe threat to public health and safety is becoming less
difficult because of newer technologies. HHS/CDC will further review
the risks posed by these technologies.
One additional public commenter thanked the Federal Government for
transparency regarding the criteria for adding/delisting agents and
toxins and strongly supported the continued use of these criteria and
processes. Another commenter stated that a list-based approach no
longer adequately addresses the current biological threat landscape,
which includes unknown, accidental, engineered, and naturally occurring
hazardous biological agents and toxins. To address the current
biological threat landscape, the commenter stated that FSAP should take
into account transmissibility, not just pathogenicity, and should move
toward a ``tiered, risk-based program'' and away from a ``list-based
program.'' HHS/CDC thanks these commenters for their thoughts. HHS/CDC
does evaluate transmissibility in the assessments of whether to include
an agent in our list, specifically under the direction of the statute
that includes contagiousness as a criterion for inclusion. Also, FSAP
derives its regulatory authority from section 351A(a)(1) of the Public
Health Service Act (42 U.S.C. 262a(a)(1)), which states that HHS/CDC
must maintain a list of select agents and toxins. HHS/CDC may consider
additional tiering to the list of select agents and toxins at the next
biennial review.

D. Retaining Tier 1 Designation of Botulinum Neurotoxin Producing
Species of Clostridium

Botulinum neurotoxin, which causes botulism, is a Tier 1 select
toxin, and botulinum neurotoxin producing species of Clostridium are a
Tier 1 select agent, regulated by HHS/CDC. In the 2024 proposed rule,
HHS/CDC requested comment on the proposal to retain botulinum
neurotoxin producing species of Clostridium as an HHS select agent, but
no longer designate it as a Tier 1 agent because the organism itself
does not normally cause disease. Botulinum neurotoxin would still be
designated as a Tier 1 toxin. HHS/CDC received mixed reactions and a
total of 14 comments on whether to downgrade botulinum neurotoxin
producing species of Clostridium from a Tier 1 agent, while keeping it
as an HHS select agent.
Nine commenters supported downgrading the agent from Tier 1, three
opposed the change, and two comments requested clarification of when
nucleic acids that encode for toxic forms of botulinum neurotoxin would
be considered Tier 1 or non-Tier 1. One commenter stated the most
compelling rationale for no longer designating the agent as Tier 1 is
that public health outbreaks with this organism are not likely or
projected to be particularly disruptive.
Three commenters did not support the change. They stated that no
longer designating botulinum neurotoxin producing species of
Clostridium as a Tier 1 select agent--while keeping botulinum
neurotoxin as a Tier 1 toxin--would introduce ambiguity to procedures
related to storage, possession, use, and in the event of an accidental
release. One commenter stated that if the neurotoxin remains as

[[Page 101946]]

a Tier 1 agent and regulatory requirements are only reduced for the
organism, it could potentially cause violations relating to an entity
producing the toxin in an unregulated manner.
One commenter recommended that if botulinum neurotoxin remains a
Tier 1 agent, then botulinum neurotoxin producing species of
Clostridium should also remain as Tier 1. Another commenter pointed out
that HHS/CDC would need to provide extensive guidance regarding
differentiating between experiments or steps in experiments that
include both the agent and toxin that require Tier 1 personnel and
practices versus non-Tier 1 personnel and practices if this change were
to take effect. Both commenters recommended that the agent, toxin, and
regulated nucleic acids all be regulated as either non-Tier 1 or Tier 1
because regulating the related materials differently would create a
substantial administrative burden to registered entities.
HHS/CDC agrees that public health outbreaks are unlikely to occur
with botulinum neurotoxin producing species of Clostridium. Per
Executive Order 13546, ``Optimizing the Security of Biological Select
Agents and Toxins in the United States,'' botulinum neurotoxin
producing species of Clostridium do not pose a great risk of deliberate
misuse with the most significant potential for mass casualties, and
therefore do not meet the standard of Tier 1. However, in accordance
with several other comments, HHS/CDC agrees that downgrading the agent
(or nucleic acids encoding for toxic forms of botulinum neurotoxin)
from Tier 1, while continuing to regulate botulinum neurotoxin as a
Tier 1 toxin would require registered entities to differentiate between
the applicable regulatory requirements, which may cause confusion.
Likewise, establishing different regulatory standards for the select
agent and related toxin would create challenges for HHS/CDC in
assessing compliance. The agent has the inherent ability to produce
Tier 1 toxin. In consideration of the logistical challenges raised in
the comments referenced above, HHS/CDC will continue to regulate
botulinum neurotoxin producing species of Clostridium as a Tier 1
select agent.

E. No Addition of Hantaviruses

In response to the 2024 proposed rule, HHS/CDC received nine public
comments that unanimously supported the proposal to not add
Hantaviruses [Sin Nombre virus (SNV), Andes virus (ANDV), Hantaan virus
(HTNV), and Dobrava virus (DOBV)] to the select agent and toxins list.
Eight commenters did not offer a rationale or evidence for their
stance; however, one commenter stated that because there is no evidence
of sustained person-to-person transmission of SNV, ANDV, HTNV, or DOBV,
they concurred with the proposal not to add these viruses to the select
agent list. Given the limited direct person-to-person transmission and
difficulty propagating in a laboratory setting, it is unclear whether
Hantaviruses would pose a severe threat to public health and safety. 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, as proposed and in addition to the unanimous support for not
adding these agents via public comment, HHS/CDC will not be adding SNV,
ANDV, HTNV, and DOBV as HHS select agents.

F. Toxin Review: Changes to Exclusion Limits for Short, Paralytic Alpha
Conotoxins

In response to the 2024 proposed rule, HHS/CDC received eight
public comments that unanimously supported the proposal to increase the
exclusion amount for short, paralytic alpha conotoxins from 100 mg to
200 mg. HHS/CDC proposed this change 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.
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 toxins on public health.
HHS/CDC reviewed the DHS models, and the lethal doses of conotoxins are
comparable to other regulated toxins with a much higher permissible
amount. Based on the DHS model and the public comments mentioned above,
HHS/CDC is raising the exclusion limit for conotoxin from 100 mg to 200
mg as proposed.

G. Designation of Nipah virus as a Tier 1 Select Agent

In the 2024 proposed rule, HHS/CDC sought public comment on whether
Nipah virus should be identified as a Tier 1 select agent because of
its human transmissibility, high case fatality rate, low infectious
dose, high severity of illness, and severity of long-term effects.
HHS/CDC received a total of 10 comments on this proposal. One
commenter was in favor of designating Nipah virus as a Tier 1 select
agent, especially given the known person-to-person transmissibility of
the virus. There were nine commenters against this change. Eight of
these commenters stated the justification is not sufficient support for
designating Nipah virus as a Tier 1 select agent over other agents on
the select agent list that are Risk Group 4 pathogens. One commenter
thought it was unclear what value the Tier 1 designation would have for
Nipah virus.
CDC disagrees with these commenters. Executive Order 13546,
``Optimizing the Security of Biological Select Agents and Toxins in the
United States,'' directs the HHS Secretary to designate a subset of
select agents and toxins as Tier 1 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. Nipah virus has high human
transmissibility; a high case fatality rate (estimated between 40-
100%); a low infectious dose (ranging from 10\1\-10\7\ plaque forming
units depending on route of infection); high severity of illness; and
severe long-term effects, including neurological complications
including encephalopathy, cranial nerve palsies, and dystonia (Sejvar
et al., 2007 and Lo et al., 2008).
For these reasons, HHS/CDC is designating Nipah virus as a Tier 1
select agent.

H. Addition of a Footnote to the HHS Select Agent and Overlap Select
Agent List

In the 2024 proposed rule, HHS/CDC received one public comment that
supported the proposal to add a footnote to the list of HHS and Overlap
select agents indicating that the current ICTV nomenclature for select
agent viruses, if different from that published in the HHS regulations,
will be available on the FSAP website (<a href="https://www.selectagents.gov">https://www.selectagents.gov</a>).
This commenter stated that the FSAP website is a good place to provide
this information. As proposed, HHS/CDC will proceed with adding a
footnote to the list for HHS and Overlap select agents for this
purpose.

I. Summary of Final Rule Provisions

In summary of the discussions in section II. of this rule, HHS/CDC
is finalizing these revisions to the Federal Select Agent Program at 42
CFR part 73:

[[Page 101947]]

<bullet> Remove Brucella abortus, Brucella melitensis, and Brucella
suis from the select agent list.
<bullet> Update the nomenclature of select agents:
[cir] Change ``SARS coronavirus (SARS-CoV)'' to ``Severe acute
respiratory syndrome coronavirus (SARS-CoV)'' to correct the
nomenclature;
[cir] Rename the exclusion of ``South American genotype of Eastern
Equine Encephalitis virus'' to ``Madariaga virus'';
[cir] Rename the exclusion of ``West African Clade of Monkeypox
virus'' to ``clade II monkeypox virus'';
[cir] Rename Ebola virus to Ebolavirus in accordance with the
recent taxonomic change by the International Committee on Taxonomy of
Viruses (ICTV);
<bullet> Retain nomenclature of monkeypox virus;
<bullet> Retain designation of botulinum neurotoxin producing
species of Clostridium as a Tier 1 agent;
<bullet> No addition of Hantaviruses: specifically not adding Sin
Nombre virus (SNV), Andes virus (ANDV), Hantaan virus (HTNV), and
Dobrava virus (DOBV) to the select agent list;
<bullet> Increase the exclusion amount for short, paralytic alpha
conotoxins from 100 mg to 200 mg;
<bullet> Designate Nipah virus as a Tier 1 Select agent;
<bullet> Add a footnote to the list for HHS and Overlap select
agents indicating that the current nomenclature will be available on
the FSAP website (<a href="https://www.selectagents.gov">https://www.selectagents.gov</a>).

III. Alternatives Considered

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.
This ensures scientific advancements and gained knowledge are applied
to each agent and toxin on the list.
Below are reasonable regulatory alternatives considered regarding
key individual provisions listed in this final rule.
This final rule contains several updates to outdated nomenclature
of agents, including monkeypox virus, Severe acute respiratory syndrome
coronavirus (SARS-CoV), and Ebolavirus. Retaining outdated nomenclature
is not scientifically accurate and causes confusion when organizations
seek to be in compliance with the regulations. Retaining outdated
nomenclature can also cause discrepancies between HHS/CDC and other
global health organizations. There is a low, one-time cost associated
with updating nomenclature. The alternative of finalizing the rule
without the proposed changes, i.e., retaining outdated nomenclature, is
not feasible or accurate.
Several changes in this final rule also ensure continued compliance
with E.O. 13546.
If HHS/CDC were to retain Nipah virus without a Tier 1 designation,
the select agent and toxin list would have an agent that has a great
risk of deliberate misuse with the potential for mass casualties, like
other Tier 1 select agents, but without the additional provisions
outlined for Tier 1 select agents and toxins. These additional
provisions include advanced security even compared to non-Tier 1
agents, laboratory personnel enrollment in an entity-specific
Occupational Health Program, and that entity-specific risk assessments
include Nipah virus as a Tier 1 agent. Not having Nipah virus
designated as Tier 1 select agent could potentially result in entities
or personnel handling the agent incorrectly, causing public health,
biosafety, and biosecurity concerns. It also would not enable FSAP to
ensure and require compliance with the enhanced Tier 1 biosafety and
biosecurity requirements provided for in the regulations.
All entities currently registered with FSAP for Nipah virus are
also registered for other Tier 1 select agents and toxins. Therefore,
these entities have Tier 1 provisions in place already that can be
applied to Nipah virus. If HHS/CDC were to retain Nipah virus as a
select agent without Tier 1 designation, the department and agency
would be out of compliance with E.O. 13546. It could also potentially
cause public health and biosecurity concerns in that the agent is not
handled appropriately. Nipah virus has high human transmissibility; a
high case fatality rate (estimated between 40-100%); a low infectious
dose; high severity of illness; and severe long-term effects.
Along similar reasoning, new models from DHS illustrate the lethal
doses of conotoxins are comparable to other regulated toxins with a
much higher permissible amount. The alternative to not raising the
permissible toxin limit for short, paralytic alpha conotoxins would
lead to irregularities of regulatory application as it pertains to
select toxins. Keeping the permissible toxin limit at 100 mg for short,
paralytic alpha conotoxins could prevent research and advancement of
understanding the select toxin, with no advancement on biosafety and
biosecurity. The raised permissible toxin limit of 200 mg will allow
more research to occur with the select toxin with no effect on public
health and safety. It is important that HHS/CDC considers new data
while reviewing the select agent and toxin list to ensure the list is
in accordance with criteria and considerations as articulated in 42
U.S.C. 262a.
Similarly, the final rule does not include adding Hantaviruses
(i.e., Sin Nombre virus (SNV), Andes virus (ANDV), Hantaan virus
(HTNV), and Dobrava virus (DOBV)) to the list as was initially proposed
in the ANPRM. Adding Hantaviruses to the list would lead to the agency
regulating agents that are not proven to pose a severe threat to public
health and safety. Hantaviruses have limited direct person-to-person
transmission and are difficult to propagate in a laboratory setting. At
this time, research shows it is not certain that Hantaviruses require
any regulation in accordance with the criteria and considerations as
articulated in 42 U.S.C. 262a. If FSAP were to begin regulating
Hantaviruses, there would be costs associated with onboarding,
inspecting, and managing those entities that would be required to
register with FSAP, with no current need to regulate the agents.
The most significant impact of this rule is the delisting of
Brucella species, and HHS/CDC has carefully considered the alternative
of delisting the agents, which would be retaining the agents on the
list and continuing regulating these agents.
Retaining the Brucella species on the list has several economic,
agricultural, and economic effects with little biosecurity benefit.
Most notably, retaining Brucella species on the list prevents
researchers from progressing advancement of science with regards to
study of the agents and development of countermeasures for this agent
by subjecting these laboratories to FSAP's regulatory authority. These
agents are designated as Risk Group 3 agents, meaning entities and
organizations will continue working with these agents at the
appropriate biosafety level (Biosafety Level 3), as outlined in the
national standard Biosafety in Microbiological and Biomedical
Laboratories, 6th edition.
Continuing regulation of Brucella melitensis, suis, and abortus has
a one-time cost of approximately $29k to an entity that wishes to
register with FSAP for work with these agents. This cost to the
regulated community, due to the reasons listed above, does not enhance
biosafety and biosecurity, and may be a regulatory burden to entities
that wish to advance understanding of the agent and research medical
countermeasures.
There is no alternative to foregoing review of the select agent and
toxin list.

[[Page 101948]]

This rulemaking is intended to meet 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. CDC conducts
the biennial review in consultation with CDC's Intragovernmental Select
Agents and Toxins Technical Advisory Committee (ISATTAC). An
alternative to the rule was to not delist three select agents, not
raise the exclusion amount of a regulated toxin, not update
nomenclature, and not add the Tier 1 designation to a select agent.
Retaining the Brucella species would maintain the current status quo;
it does not consider that these agents no longer pose a severe threat
to public health and safety, does not promote better research and
vaccine development, and does not align with USDA's decision to delist
the Brucella agents. Additionally, the alternative to not amend the
select agent list is inconsistent with USDA's rule, creating regulatory
conflict. In addition, this option is not consistent with the public
comment received to support amending the select agent list.
After carefully considering the technical input of subject-matter
experts, both within the Federal Government and from public comments,
and recommendations from Federal advisory groups, HHS/CDC is finalizing
the changes listed in section II, part I (Summary of Final Rule
Provisions) above to the list of select agents and toxins.

IV. Required Regulatory Analyses

The HHS/CDC modifications to the list of select agents and toxins
addressed in this rule will benefit producers, research and reference
laboratories, and state and Federal oversight agencies, while also
maintaining adequate program oversight of select agents and toxins.
Specifically, HHS/CDC is removing Brucella abortus, Brucella
melitensis, and Brucella suis from the select agent and toxin list;
updating the nomenclature for several select agents (``SARS coronavirus
(SARS-CoV),'' removing the exclusion regarding ``South American
genotype of Eastern Equine Encephalitis virus,'' renaming the exclusion
regarding ``West African Clade of Monkeypox virus,'' and ``Ebola
virus''); retaining the nomenclature of Monkeypox virus; retain the
Tier 1 designation of Botulinum neurotoxin producing species of
Clostridium; no addition of Hantaviruses to the current select agent
and toxin list; increase the exclusion amount for short, paralytic
alpha conotoxins from 100 mg to 200 mg; and designating Nipah virus as
a Tier 1 Select Agent. HHS/CDC is also adding a footnote to the list
for HHS and Overlap select agents indicating that the current
nomenclature will be available on the website (<a href="http://www.selectagents.gov">www.selectagents.gov</a>).
Currently, 236 entities are registered with the Federal Select
Agent Program (FSAP). Of these entities, there are 13 private entities,
30 Federal entities, 42 commercial entities, 84 academic entities, and
67 state entities (registered with either APHIS or CDC, depending on
the select agents and toxins they work with). Less than 4 percent of
all firms operating within these North American Industry Classification
categories are considered to be small entities. This final rule 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 the
costs of complying with the regulatory requirements. As an example of
losses that can occur due to a select agent release, the October 2001
anthrax attacks caused 5 fatalities and 17 illnesses, disrupted
business and government activities (including $2 billion in lost
revenues for the U.S. 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.
HHS has examined the impacts of this rule as required by Executive
Order 12866 on Regulatory Planning and Review (September 30, 1993),
Executive Order 13563 on Improving Regulation and Regulatory Review
(January 18, 2011), Executive Order 14094, entitled ``Modernizing
Regulatory Review'' (April 6, 2023), the Regulatory Flexibility Act
(RFA) (September 19, 1980, Pub. L. 96-354), section 1102(b) of the
Social Security Act, section 202 of the Unfunded Mandates Reform Act of
1995 (March 22, 1995; Pub. L. 104-4), and Executive Order 13132 on
Federalism (August 4, 1999). This final rule does not meet the criteria
set forth in 5 U.S.C. 804(2) under the Congressional Review Act.

A. Executive Orders 12866, 13563, and 14094

Executive Orders 12866 and 13563 direct agencies to assess all
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety effects, distributive impacts, and equity). Executive
Order 14094 (the Modernizing E.O.) amends section 3(f) of Executive
Order 12866 (Regulatory Planning and Review). The amended section 3(f)
of Executive Order 12866 defines a ``significant regulatory action'' as
an action that is likely to result in a rule: (1) having an annual
effect on the economy of $200 million or more in any 1 year (adjusted
every 3 years by the Administrator of Office of Information and
Regulatory Affairs (OIRA) for changes in gross domestic product), or
adversely affect in a material way the economy, a sector of the
economy, productivity, competition, jobs, the environment, public
health or safety, or State, local, territorial, or Tribal governments
or communities; (2) creating a serious inconsistency or otherwise
interfering with an action taken or planned by another agency; (3)
materially altering the budgetary impacts of entitlement grants, user
fees, or loan programs or the rights and obligations of recipients
thereof; or (4) raise legal or policy issues for which centralized
review would meaningfully further the President's priorities or the
principles set forth in this Executive order, as specifically
authorized in a timely manner by the Administrator of OIRA in each
case. OIRA has determined that this rule is significant.
Statement of Need
As discussed above, HHS/CDC is removing Brucella abortus, Brucella
melitensis, and Brucella suis from the select agent list; updating the
nomenclature for several select agents (``SARS coronavirus (SARS-
CoV),'' the exclusion regarding ``South American genotype of Eastern
Equine Encephalitis virus,'' the exclusion regarding ``West African
Clade of Monkeypox virus,'' and ``Ebola virus''); retaining the
nomenclature of Monkeypox virus; retaining the Tier 1 designation of
Botulinum neurotoxin producing species of Clostridium; not adding
Hantaviruses to the current select agent list; increasing the exclusion
amount for short, paralytic alpha conotoxins from 100 mg to 200 mg; and
designating Nipah virus as a Tier 1 Select Agent. HHS/CDC is also
adding a footnote to the list for HHS and Overlap select agents
indicating that the current nomenclature will be available on the
website (<a href="http://www.selectagents.gov">www.selectagents.gov</a>).
Some of the regulatory changes described in the preamble and
reported below are a minor in nature, and as

[[Page 101949]]

such, are expected to have minimal impact on the costs and benefits of
current regulations, except for the one-time costs of updating official
documents for CDC. These regulatory changes are the updates to the
nomenclature for several select agents (``SARS coronavirus [SARS-
CoV],'' the exclusion regarding ``South American genotype of Eastern
Equine Encephalitis virus,'' the exclusion regarding ``West African
Clade of Monkeypox virus.'' and ``Ebola virus); retaining the
nomenclature of Monkeypox virus, retaining the Tier 1 designation of
Botulinum neurotoxin producing species of Clostridium; no addition of
Hantaviruses to the current select agent list; increasing the exclusion
amount for short, paralytic alpha conotoxins from 100 mg to 200 mg; and
designating Nipah virus as a Tier 1 Select Agent.
This final rule changes the regulatory baseline by removing
Brucella abortus, Brucella melitensis, and Brucella suis from the
select agent list. As of July 2024, of the 236 registered entities with
FSAP, 112 were registered for select agents and toxins including
Brucella abortus, melitensis, and/or suis, and three of those entities
were registered for only Brucella species. CDC expects the three
entities registered for only Brucella species will deregister from
FSAP, which HHS/CDC expects will cause minimal savings for these
laboratories, as well as CDC. The remaining 109 entities will likely
submit amendments to their registrations to remove the delisted agents
while maintaining the rest of their registration. Therefore, HHS/CDC
expects no change in the costs for these entities; there is no cost to
deregister with FSAP. Because of the small number of entities that will
deregister due to the delisting of Brucella species, the cost-savings
to the government will be minimal, roughly a net value (benefits-costs)
of $8,795.78 in one-time cost savings.
Costs
This final rule does not impose any mandatory costs on the public
and benefits laboratories who choose to develop research using Brucella
abortus, Brucella melitensis, and Brucella suis. Nonetheless, the
changes in this rule will have a minimal economic impact on CDC due to
the process of updating official documentation for the implementation
of the changes listed in this final rule.
To estimate the cost to CDC of including the changes listed in this
final rule in official documents, HHS/CDC assumed that 1 GS-14, step 5
employee and one GS-15, step 5 employee each spend 40 hours (i.e., 80
hours in total) for any updates to cite the language in this final
rule. The hourly wage rates for two employees based in Washington-
Baltimore-Arlington, DC-MD-VA-WV-PA are $75.70 (GS-14) and $89.03 (GS-
15).\1\ To account for the non-wage benefits, we multiplied the wage
cost by two to result in a total cost estimate of $13,178 (table 1).
---------------------------------------------------------------------------

\1\ U.S. Office of Personnel and Management. <a href="https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/2024/general-schedule-gs-salary-calculator/">https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/2024/general-schedule-gs-salary-calculator/</a> accessed on September 4,
2024.

Table 1--Summary of the One-Time Costs in 2024 USD To Update Official Documents for Department of State (DOS),
Centers for Disease Control and Prevention (CDC) Costs From Updating Official Documents With the Changes in This
Final Rule
----------------------------------------------------------------------------------------------------------------
Multiplier non-
Agency Cost components Hourly wage wage benefits Total
rate \2\ and overhead
----------------------------------------------------------------------------------------------------------------
CDC................................ 80 hours split between GS- $82.4 2 $13,178
14, step 5, and GS-15,
step 5 levels.
----------------------------------------------------------------------------
Total.......................... ........................... .............. .............. 13,178
----------------------------------------------------------------------------------------------------------------

The changes in this final rule that are minor in nature and should
not result in an additional regulatory burden to regulated entities.
Instead, they should help reduce costs by reducing confusion regarding
the requirements for the possession, use, and transfer of biological
select agents and toxins.
---------------------------------------------------------------------------

\2\ U S Office of Personnel Management: General Schedule
(<a href="http://opm.gov">opm.gov</a>).
---------------------------------------------------------------------------

The elimination of Brucella abortus, Brucella melitensis, and
Brucella suis from the select agents and toxins list should not result
in additional regulatory burden for CDC or regulated entities as this
change would imply less regulatory burden. However, one concern about
this reduction in regulatory burden is that it could cause costs or
losses to the general public by increasing the risk of Brucella
abortus, Brucella melitensis, and Brucella suis being accessed without
authorization, stolen, lost, or released. Although this cost cannot be
measured until after the regulation has been applied, HHS/CDC expects
that the risk of Brucella abortus, Brucella melitensis, and Brucella
suis being accessed without authorization, stolen, lost, or released
would be minimal as the current recommended best practices in place to
mitigate these biosafety and biosecurity risks (Biosafety in
Microbiological and Biomedical Laboratories) will remain in place.
USDA's prevention and eradication efforts against Brucellosis from
livestock in the United States through the National Bovine Brucellosis
Surveillance Plan and the National Brucellosis Eradication program will
continue even with the changes in this rule.
Another concern linked to the reduction in regulatory burden to
agencies and laboratories is that it could increase cost to the general
public by increasing the risk of Brucella abortus, Brucella melitensis,
and Brucella suis becoming an agent of interest to be used as a
bioweapon. Although this risk cannot be measured by HHS/CDC currently,
HHS/CDC expects this risk to be minimal as recent literature indicates
that Brucella's ``minimal mortality, availability of treatment options,
protracted inoculation period and the emergence of new, more virulent
potential weapons means that its inclusion among agents of bioterrorism
is nowadays mainly of historical significance.'' \3\
---------------------------------------------------------------------------

\3\ Pappas, G., Panagopoulou, P., Christou, L., & Akritidis, N.
(2006). Biological weapons: Brucella as a biological weapon.
Cellular and molecular life sciences CMLS, 63, 2229-2236.
---------------------------------------------------------------------------

Increasing the exclusion limits for short paralytic alpha
conotoxins will have a negligible impact on costs for regulated
entities. There are only four registered entities currently working
with these conotoxins, and increasing

[[Page 101950]]

the exclusion limit will allow for additional research and testing
without the additional burden of select agent and toxin regulatory
requirements.
Change to the designation of Nipah virus as a Tier 1 select agent
will have a negligible impact on costs for regulated entities. All
eight of the entities that are currently registered for Nipah virus are
already registered for other Tier 1 select agents; therefore they are
already complying with the additional Tier 1 requirements and will not
incur additional costs with this change.
Benefits
HHS found the benefits of this rulemaking to outweigh the costs to
regulated entities as all the changes described in this final rule have
a zero cost to regulated entities. Furthermore, these changes are
likely to reduce regulated entities' costs by simplifying their
processes and reducing some of the regulatory burden. HHS/CDC is unable
to quantify the cost reductions to regulated entities due to the minor
changes but expects this final rule will potentially simplify processes
for them. Nonetheless, at a minimum, costs of these changes are zero
for regulated entities, thus any simplification of processes coming out
of this change implies a gain.
As of July 2024, of the 236 registered entities with APHIS and CDC,
112 were registered for select agents and toxins including Brucella
abortus, melitensis, and/or suis, and three of those entities are
registered for only Brucella species. CDC expects the three entities
registered for only Brucella species will deregister from FSAP, which
HHS/CDC expects to cause small savings for these entities. Although
FSAP registration does not have a direct cost for regulated entities,
HHS/CDC estimates that it takes 12 hours of labor a week for eight
months to perform the registration processes required to get an FSAP
registration. These activities are usually performed by a Responsible
Official/Biosafety Officer or an Alternate Responsible Official/
Biosafety Officer. The GS scale for these professionals typically
ranges from GS-9 to GS-14. Assuming a GS-14 scale, the hourly wage rate
based in Washington-Baltimore-Arlington, DC-MD-VA-WV-PA is $75.70.
Thus, the estimated one-time cost of registration with FSAP for an
entity is $29,069. This estimated one-time cost savings will apply to
any entities not registered with FSAP that wish to work with Brucella
species. Renewal of registration with FSAP is a negligible cost as the
process takes less than 10 minutes. Because three entities are
currently registered solely for Brucella species, the exclusion of
Brucella abortus, Brucella melitensis, and Brucella suis from the
select agent list means they will not need to participate in the
registration renewal process, which is a negligible cost.
HHS/CDC expects that the deregistration of the three entities
registered only for Brucella species with FSAP will also cause small
one-time cost-savings to CDC, as CDC personnel will no longer follow
these entities throughout the registration process. HHS/CDC estimates
that CDC personnel spend about three hours a week for six months
reviewing laboratories' Standard Operating Procedures (SOPs) for
entity's registration applications to FSAP. Assuming that the CDC staff
reviewing SOPs is GS-13 step 5, the hourly salary in 2024 dollars would
be $64.06, thus the one-time cost savings to CDC of reviewing the SOPs
required for one entity's registration is $1,153.08, and this implies a
total of $3,459.24 in cost savings for CDC of not going through the
registration process of the three entities that would deregister after
the publication of this rule.
In addition to these cost savings CDC will also have cost savings
from not having to perform inspections on the three entities that are
ending their FSAP registrations as a result of the exclusion of
Brucella abortus, Brucella melitensis, and Brucella suis from the
select agent list. Assuming that the personnel performing the
inspections are a GS-12 step 5, and a GS-13 step 5 inspectors, the
hourly wage is $53.87, and $64.06, respectively. Using an overhead
multiplier of 2 to take into account non-wage benefits, and considering
the travel costs of inspections, HHS/CDC estimates one-time costs
savings of $10,564.18 per inspection not performed per entity (table
2). Since each entity goes through at least one inspection during
registration, HHS/CDC estimates CDC will have a cost savings of at
least $31,692.54 due to inspections not performed for the three
entities deregistering from FSAP.

Table 2--Estimated Annual CDC Cost-Savings in 2024 USD for Inspection of Each Facility Only Working With Brucella
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of inspections Number of hours spent Average hourly Overhead One-time
Type of CDC staff Number of staff per year per inspection wage rate \4\ multiplier annual benefit
--------------------------------------------------------------------------------------------------------------------------------------------------------
GS-12 (step 5)..................... 1.................... 0.5.................. 40................... $53.87 2 $4,309.6
GS-13 (step 5)..................... 1.................... 0.5.................. 40................... 64.06 2 5,124.8
--------------------------------------------------------------------------------------------------------------------
Total.......................... ..................... ..................... ..................... .............. .............. 9,438.4
--------------------------------------------------------------------------------------------------------------------------------------------------------
Travel costs....................... Airfare \5\.......... 417.79/per person.... Hotel, food, lodging 145.10/per person 1125.78
\6\.
--------------------------------------------------------------------------------------------------------------------
Total (Personnel + Travel)..... ..................... ..................... ..................... .............. .............. 10,564.18
--------------------------------------------------------------------------------------------------------------------------------------------------------

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, should recognize distributive impacts and equity, to the
extent permitted by law. HHS/CDC developed this final 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

[[Page 101951]]

exchange of ideas. HHS/CDC developed this final rule in a manner
consistent with these requirements. In administering FSAP, HHS, along
with USDA, regularly interact with the affected registered entities via
email, phone, online webinars, through the eFSAP information system,
and through designated points of contact at registered entities. All
changes result from entity questions received or interaction with
registered entities who have contacted FSAP when they had questions or
regulatory interpretation requests. Therefore, HHS/CDC believes this
final rule serves the public interest. Additionally, HHS/CDC encouraged
public participation and informed registered entities of the proposed
rule via a Select Agent (SA) Gram and a GovD message to ensure they
were aware and had a chance to provide public comments. The FSAP
website (<a href="http://www.selectagents.gov">www.selectagents.gov</a>) was updated to share the proposed
changes and provided a link to web visitors so that they could review
and provide comments on the proposed rule. Lastly, HHS/CDC emailed
outreach notes summarizing the proposed rule directly to national
partner organizations (e.g., the Association of Public Health
Laboratories, American Society for Microbiology, American Biological
Safety Association) so that they could share among their constituents.
As discussed above, HHS/CDC carefully reviewed and considered public
comments in the development of this final rule.
---------------------------------------------------------------------------

\4\ U.S. Office of Personnel Management: General Schedule
(<a href="http://opm.gov">opm.gov</a>).
\5\ Bureau of Transportation Statistics: Air Fares <radical>
Bureau of Transportation Statistics (<a href="http://bts.gov">bts.gov</a>).
\6\ FY 2024 Federal Per Diem Rates: FY 2024 Federal Per Diem
Rates (<a href="http://federalpay.org">federalpay.org</a>).
---------------------------------------------------------------------------

B. The Regulatory Flexibility Act (RFA), as Amended by the Small
Business Regulatory Enforcement Fairness Act (SBREFA)

HHS/CDC examined the impacts of this final rule under the
Regulatory Flexibility Act (5 U.S.C. 601-612). Unless HHS/CDC certifies
that the final rule is not expected to have a significant economic
impact on a substantial number of small entities, the RFA, as amended
by SBREFA, requires agencies to analyze regulatory options that would
minimize any significant economic impact of a rule on small entities.
Currently, 236 entities are registered with FSAP. Of these entities,
there are 13 private entities, 30 Federal entities, 42 commercial
entities, 84 academic entities, and 67 state entities (registered with
either APHIS or CDC, depending on the select agents and toxins they
work with). Less than 4 percent of all firms operating within these
North American Industry Classification System (NAICS) categories are
considered to be small entities. HHS/CDC estimates that 13 entities
will be impacted by the changes in this rule. Of these 13 entities,
which are not considered small, 4 are associated with colleges,
universities, and professional schools; 2 are categorized as research
and development in biotechnology; and 7 are part of research and
development in the physical, engineering, and life sciences. Applying
NAICS' estimation of less than 4 percent of entities classified as
small, we find that not even one small entity will be affected by the
changes in this rule. Based on our analysis as described above, we
certify that this final rule will not have a significant economic
impact on a substantial number of small entities within the meaning of
the RFA. In addition, no public comments were received from any small
entities on the RFA section.
Based on the information above, this regulatory action is not a
major rule as defined by sec. 804 of the Small Business Regulatory
Enforcement Fairness Act of 1996. This final 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
U.S.-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 determined that the Paperwork
Reduction Act does apply to information collection and recordkeeping
requirements included in this rule. This final rule focuses on the
select agent and toxins list. Any changes to burden hours caused by the
removal of Brucella abortus, Brucella suis, and Brucella melitensis
from the list of select agents and toxins will be submitted for
consideration by OMB under the existing approved PRA package
(Possession, Use, and Transfer of Select Agents and Toxins (42 CFR part
73)). Other changes put forth in this final rule, i.e., updating entity
registrations to reflect the nomenclature updates to the list, will be
instituted by FSAP, resulting in no additional paperwork for the
regulated community.

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 reviewed this final rule in accordance with Executive Order
13132 regarding federalism and 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 issuing this rule consistent with
the Federal Plain Writing Act guidelines.

V. References

Government Accountability Office. 2023. Public Health Preparedness:
HHS Could Improve Oversight of Research Involving Enhanced Potential
Pandemic Pathogens (GAO-23-105455). <a href="https://www.gao.gov/products/gao-23-105455">https://www.gao.gov/products/gao-23-105455</a>
Lo, M., et al. The Emergence of Nipah virus, a Highly Pathogenic
Paramyxovirus. J Clin Virol, 2008. 43(4): p. 396-400.
Olsen, S., et al. Biosafety Concerns Related to Brucella and its
Potential Use as a Bioweapon. Applied Biosafety, 2018. 23(2): p. 77-
90. Biosafety Concerns Related to Brucella and Its Potential Use as
a Bioweapon [verbar] Applied Biosafety (<a href="http://liebertpub.com">liebertpub.com</a>).
Sejvar, J., et al. Long-term Neurological and Functional Outcome in
Nipah virus Infection. Ann Neurol. 2007 Sep;62(3): p. 235-42.
Ulaeto, D., et al. New Nomenclature for mpox (monkeypox) and
Monkeypox Virus Clades. The Lancet: Infectious Diseases, 2023.
23(3): pg 273-275. <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099">https://www.thelancet.com/journals/laninf/article/PIIS1473-3099</a>(23)00055-5/fulltext.

List of Subjects in 42 CFR Part 73

Biologics, Packaging and containers, Penalties, Reporting and
recordkeeping requirements, Transportation.

For the reasons discussed in the preamble, HHS amends 42 CFR part
73 as follows:

[[Page 101952]]

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.

0
2. Section 73.3 is amended by:
0
a. Revising paragraph (b);
0
b. In paragraph (d)(7), removing the text ``100 mg of Conotoxins'' and
adding in its place the text ``200 mg of Conotoxins''; and
0
c. Revising paragraph (d)(12).
The revisions read as follows:

Sec. 73.3 HHS select agents and toxins.

* * * * *
(b) HHS select agents and toxins \1\ are:
(1) Abrin.
(2) Bacillus cereus Biovar anthracis.*
(3) Botulinum neurotoxins.*
(4) Botulinum neurotoxin producing species of Clostridium.*
(5) 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>).\2\
(6) Coxiella burnetii.
(7) Crimean-Congo hemorrhagic fever virus.
(8) Diacetoxyscirpenol.
(9) Eastern equine encephalitis virus.
(10) Ebolavirus *
(11) Francisella tularensis.*
(12) Lassa fever virus.
(13) Lujo virus.
(14) Marburg virus.*
(15) Monkeypox virus.
(16) 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).
(17) Ricin.
(18) Rickettsia prowazekii.
(19) Severe acute respiratory syndrome coronavirus (SARS-CoV).
(20) SARS-CoV/SARS-CoV-2 chimeric viruses resulting from any
deliberate manipulation of SARS-CoV-2 to incorporate nucleic acids
coding for SARS-CoV virulence factors.
(21) Saxitoxin.
(22) South American hemorrhagic fever virus: Chapare.
(23) South American hemorrhagic fever virus: Guanarito.
(24) South American hemorrhagic fever virus: Junin.
(25) South American hemorrhagic fever virus: Machupo.
(26) South American hemorrhagic fever virus: Sabia.
(27) Staphylococcal enterotoxins (subtypes A,B,C,D,E).
(28) T-2 toxin.
(29) Tetrodotoxin.
(30) Tick-borne encephalitis virus: Far Eastern subtype.
(31) Tick-borne encephalitis virus: Siberian subtype.
(32) Kyasanur Forest disease virus.
(33) Omsk haemorrhagic fever virus.
(34) Variola major virus (Smallpox virus).*
(35) Variola minor virus (Alastrim).*
(36) Yersinia pestis.*
\1\ Please refer to <a href="https://www.selectagents.gov">https://www.selectagents.gov</a> for current
information on historical or proposed nomenclature for the HHS select
agents on the list.
\2\ 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.
* * * * *
(d) * * *
(12) Madariaga virus and any Clade II Monkeypox provided that the
individual or entity can identify that the agent is within the
exclusion category.
* * * * *

0
3. Section 73.4 is amended by revising paragraph (b) to read as
follows:

Sec. 73.4 Overlap select agents and toxins.

* * * * *
(b) Overlap select agents and toxins \1\ are:
(1) Bacillus anthracis.*
(2) Bacillus anthracis Pasteur strain.
(3) Burkholderia mallei.*
(4) Burkholderia pseudomallei.*
(5) Hendra virus.
(6) Nipah virus.*
(7) Rift Valley fever virus.
(8) Venezuelan equine encephalitis virus.
\1\ Please refer to <a href="https://www.selectagents.gov">https://www.selectagents.gov</a> for current
information on historical or proposed nomenclature for the Overlap
select agents on the list.
* * * * *

Dated: December 11, 2024.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2024-29583 Filed 12-16-24; 8:45 am]
BILLING CODE 4163-18-P

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