Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins, 101941-101952 [2024-29583]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[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 [www.gpo.gov]
[FR Doc No: 2024-29583]


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

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.

-----------------------------------------------------------------------

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:
     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 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:
     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;
     Degree of contagiousness:
    [cir] dissemination efficacy;
    [cir] aerosol stability;
    [cir] rate of transmission;
     Availability and effectiveness of pharmacotherapies:
    [cir] available treatment;
     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:
     Removal of Brucella abortus, Brucella melitensis, and 
Brucella suis: Proposal to remove Brucella abortus, Brucella 
melitensis, and Brucella suis from the select agent list.
     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).
     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.''
     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.
     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.
     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.
     Designation of Nipah virus as a Tier 1 Select Agent: 
Proposal to designate Nipah virus as a Tier 1 select agent.
     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 (https://www.selectagents.gov) 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 https://www.selectagents.gov/efsap/using/form1/docs/eFSAP_Form_1_Amendments_Guidance_508.pdf.
    For brucellosis case reporting and national notification, please 
visit https://www.cdc.gov/brucellosis/hcp/surveillance/.
    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 https://www.cdc.gov/labs/bmbl/.

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 (https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease). This was updated in the 
International Classification of Diseases (ICD) system (https://icd.who.int/browse/2024-01/mms/en#160886685).
    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) (https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new-names). 
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 (https://www.selectagents.gov/sat/exclusions/hhs.htm). 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, https://www.who.int/news/item/28-11-2022-who-recommends-new-name-for-monkeypox-disease). 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 (https://www.selectagents.gov). 
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]]

     Remove Brucella abortus, Brucella melitensis, and Brucella 
suis from the select agent list.
     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);
     Retain nomenclature of monkeypox virus;
     Retain designation of botulinum neurotoxin producing 
species of Clostridium as a Tier 1 agent;
     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;
     Increase the exclusion amount for short, paralytic alpha 
conotoxins from 100 mg to 200 mg;
     Designate Nipah virus as a Tier 1 Select agent;
     Add a footnote to the list for HHS and Overlap select 
agents indicating that the current nomenclature will be available on 
the FSAP website (https://www.selectagents.gov).

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 (www.selectagents.gov).
    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 (www.selectagents.gov).
    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. https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/2024/general-schedule-gs-salary-calculator/ 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 
(opm.gov).
---------------------------------------------------------------------------

    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 (www.selectagents.gov) 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 
(opm.gov).
    \5\ Bureau of Transportation Statistics: Air Fares  
Bureau of Transportation Statistics (bts.gov).
    \6\ FY 2024 Federal Per Diem Rates: FY 2024 Federal Per Diem 
Rates (federalpay.org).
---------------------------------------------------------------------------

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). https://www.gao.gov/products/gao-23-105455
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 (liebertpub.com).
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. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(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 
X1CCX2PACGX3X4X5X
6CX7).\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 https://www.selectagents.gov 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 https://www.selectagents.gov 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