[Federal Register Volume 89, Number 20 (Tuesday, January 30, 2024)]
[Proposed Rules]
[Pages 5823-5842]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-01513]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. CDC-2020-0024]
42 CFR Part 73
RIN 0920-AA71
Possession, Use, and Transfer of Select Agents and Toxins;
Biennial Review of the List of Select Agents and Toxins
AGENCY: Centers for Disease Control and Prevention (CDC), Department of
Health and Human Services (HHS).
ACTION: Notice of proposed rulemaking.
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SUMMARY: In accordance with the Public Health Service Act, the
Department of Health and Human Services (HHS) Centers for Disease
Control and Prevention (CDC) reviewed the HHS list of select agents and
toxins with the potential to pose a severe threat to public health and
safety. HHS/CDC proposes to amend the list by removing three biological
agents, raising one toxin's exclusion amounts, renaming a virus,
designating a current agent as a Tier 1 agent, and removing the
designation of Tier 1 status from one agent. HHS/CDC also proposes to
clarify language and add requirements as discussed below.
DATES: Submit written or electronic comments by April 1, 2024.
ADDRESSES: You may submit comments, identified by Docket No. CDC-2020-
0024 or Regulation Identifier Number (RIN) 0920-AA71, by any of the
following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments.
Mail: Division of Regulatory Science and Compliance,
Centers for Disease Control and Prevention, 1600 Clifton Road NE,
Mailstop H21-4,
[[Page 5824]]
Atlanta, Georgia 30329, ATTN: RIN 0920-AA71.
Instructions: All submissions received must include the agency name
and RIN for this rulemaking. All relevant comments received will be
posted without change to http://www.regulations.gov, including any
personal information provided. Do not send comments by email; CDC does
not accept public comment by email.
Docket Access: For access to the docket to read background
documents or comments received, or to download an electronic version of
the notice of proposed rulemaking, go to http://www.regulations.gov.
FOR FURTHER INFORMATION CONTACT: Samuel S. Edwin Ph.D., Director,
Division of Regulatory Science and Compliance, Centers for Disease
Control and Prevention, 1600 Clifton Road NE, Mailstop H21-7, Atlanta,
Georgia 30329. Telephone: (404) 718-2000.
SUPPLEMENTARY INFORMATION: The Notice of Proposed Rulemaking (NPRM) is
organized as follows:
I. Public Participation
II. Background
A. Legal Authority
B. 2020 ANPRM
III. Summary of Proposed Changes to 42 CFR Part 73
A. Definitions
B. Removal of Brucella abortus, Brucella melitensis, and
Brucella suis
C. Botulinum Neurotoxin Producing Species of Clostridium
D. Hantaviruses
E. Toxin Review: Changes to Exclusion Limits for Short,
Paralytic Alpha Conotoxins
F. Renaming Ebola Virus to the Genus Ebolavirus
G. Designating Nipah Virus as a Tier 1 Select Agent
H. Adding a Footnote to the HHS Select Agent List
I. Discovery of Select Agents or Toxins
J. Non-Possession of Select Agents or Toxins by a Registered
Entity
K. Electronic Federal Select Agent Program (eFSAP) Information
System
L. Registration
M. Tier 1 Security Enhancements
N. Biosafety--Facility Verification
O. Biosafety--Effluent Decontamination System
P. Restricted Experiments
Q. Training
R. Records
S. Codifying Existing Policies
IV. Alternatives Considered
V. Required Regulatory Analyses
A. Executive Orders 12866,13563, and 14094
B. The Regulatory Flexibility Act
C. Paperwork Reduction Act of 1995
D. E.O. 12988: Civil Justice Reform
E. E.O. 13132: Federalism
F. Plain Language Act of 2010
VI. References
I. Public Participation
Interested persons or organizations are invited to participate by
submitting written views, recommendations, and data. Comments are
welcomed on any topic related to this notice.
In addition, HHS/CDC invites comments specifically as to whether
there are additional biological agents or toxins that should be added
or removed from the HHS list of select agents and toxins based on the
following criteria outlined under 42 U.S.C. 262a(a)(1)(B):
(1) ``The effect on human health of exposure to the agent or
toxin''
(2) ``The degree of contagiousness of the agent or toxin and the
methods by which the agent or toxin is transferred to humans''
(3) ``The availability and effectiveness of pharmacotherapies to
treat or immunizations to prevent any illness resulting from infection
by the agent or exposure to the toxin''
(4) ``Any other criteria including the needs of children and other
vulnerable populations'' and any other criteria that the commenter
believes should be considered.
Comments received, including attachments and other supporting
materials, are part of the public record and subject to public
disclosure. Commenters should not include any information in their
comments or supporting materials that they consider confidential or
inappropriate for public disclosure. HHS/CDC will carefully consider
all comments submitted in preparation of a final rule. Do not send
comments by email. CDC does not accept public comment by email.
II. Background
A. Legal Authority
Under the Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (Bioterrorism Response Act), the HHS Secretary
must establish by regulation, a list of biological agents and toxins
that have the potential to pose a severe threat to public health and
safety (42 U.S.C. 262a(a)(1)). In determining whether to include a
biological agent or toxin on the list, the Bioterrorism Response Act
requires that the HHS Secretary consider the following criteria: the
effect on human health of exposure to an agent or toxin; the degree of
contagiousness of the agent and the methods by which the agent or toxin
is transferred to humans; the availability and effectiveness of
pharmacotherapies and immunizations to treat and prevent illnesses
resulting from an agent or toxin; and any other criteria, including the
needs of children and other vulnerable populations that the HHS
Secretary deems relevant (42 U.S.C. 262a(a)(1)(B)).
Under 42 U.S.C. 262a(a)(2), the HHS Secretary must review and
republish the list of HHS select agents and toxins at least biennially.
For this review, HHS/CDC evaluated as discussed below each agent and
toxin based on: the degree of pathogenicity (ability of an organism to
cause disease); dissemination efficacy; aerosol stability; matrix
stability; ease of production; ability to genetically manipulate or
alter; severity of illness; case fatality rate; long-term health
effects; rate of transmission; available treatment; status of host
immunity (e.g. whether an individual has already been exposed to the
agent and generated an immune response); vulnerability of special
populations; decontamination and restoration (the extent remediation
efforts are needed due to agent persistence in the environment and
population); and the burden or impact on the health care system.
As noted above, the list of HHS select agents and toxins is divided
into two sections. The biological agents and toxins listed in 42 CFR
73.3 (HHS select agents and toxins) have the potential to pose a severe
threat to human health and safety and are regulated only by HHS. The
biological agents listed in 73.4 (overlap select agents and toxins)
have not only the potential to pose a severe threat to human health and
safety, but have also been determined by the USDA, pursuant to USDA's
authority under the Agriculture Bioterrorism Protection Act of 2002 (7
U.S.C. 8401), to have the potential to pose a severe threat to animals
and animal products. Accordingly, these biological agents are jointly
regulated by HHS and USDA as ``overlap'' select agents. The
Bioterrorism Response Act defines the term ``overlap agents and
toxins'' to mean biological agents and toxins that are listed pursuant
to 42 U.S.C. 262a(a)(1) and listed pursuant to 7 U.S.C. 8401(a)(1). See
42 U.S.C. 262a(l) and 7 U.S.C. 8401(l). If HHS/CDC removes any overlap
select agents from its list, these agents might still be regulated as
USDA select agents dependent on the outcome of the USDA biennial
review. The Federal Select Agent Program (FSAP) is the collaboration of
the CDC, Division of Regulatory Science and Compliance (previously
known as the Division of Select Agents and Toxins) and the USDA Animal
and Plant Health Inspection Service (APHIS), Division of Agricultural
Select Agents and Toxins to administer the select agent regulations and
coordinate federal oversight of select agents and toxins in
[[Page 5825]]
a manner to minimize the administrative burden on the regulated
community.
B. 2020 ANPRM
On March 17, 2020, we published an advance notice of proposed
rulemaking (ANPRM) (85 FR 15087) in which we stated that we were
requesting comments on whether to retain or remove three species of
Brucella (B. abortus, B. melitensis, and B. suis), Rickettsia
prowazekii, Coxiella burnetii, Bacillus anthracis (Pasteur strain),
Botulinum neurotoxin producing species of Clostridium, and Venezuelan
Equine Encephalitis Virus (VEEV) 1AB and 1C. We received 335 comments
from the ANPRM. Regarding the request for comment on whether to retain
or remove R. prowazekii, C. burnetii, B. anthracis (Pasteur strain),
Botulinum neurotoxin producing species of Clostridium, and VEEV from
the select agent and toxins list, HHS/CDC received 27 comments from
individuals, animal health groups, regulated communities and public
health associations that had mixed opinions on removing and retaining
the agents. Of the 16 commenters who supported delisting, the majority
of comments supported the delisting of C. burnetii and C. botulinum.
Six commenters believed that C. burnetii should be delisted to allow
for effective research can be conducted towards the development of
improved vaccination for livestock, diagnostics, and other livestock
management options and one commenter argued many people may have
already been exposed, approximately 60% of exposures remain
asymptomatic, and a significant portion of the population may already
have immunity. Besides the five comments that cited information found
in the ANPRM as a basis for removal, one commenter added that the
disease botulism is caused by intoxication with protein toxins,
botulinum neurotoxins, and not by intoxication with C. botulinum.
Another commenter indicated that spores of botulinum neurotoxin species
of Clostridium, used to conduct food challenge studies should be
excluded from the requirements of the regulations. There was only one
comment each in support of delisting R. prowazekii, VEEV, and B.
anthracis (Pasteur strain) that supported information found in ANPRM.
After carefully reviewing the public comments and considerations for
determining whether to include an agent or toxin on the list as
articulated in 42 U.S.C. 262a, we are proposing to retain Rickettsia
prowazeckii, Coxiella burnetii, VEEV, and B. anthracis (Pasteur strain)
from the select agents and toxins list. The additional changes we are
moving forward with in this proposed rule can be found listed below
including proposing the removal of Brucella abortus, Brucella
melitensis, and Brucella suis. We also are proposing to raise exclusion
amounts for conotoxin, renaming Ebola virus, designating Nipah virus as
a Tier 1 select agent, and removing the designation of Tier 1 status
from Botulinum neurotoxin producing species of Clostridium. We
appreciate all comments received from the ANPRM and will consider these
comments in future deliberations.
III. Summary of Proposed Changes to 42 CFR Part 73
The following changes to the list of HHS select agents and toxins
are proposed based on comments received in response to the advance
notice of proposed rulemaking (85 FR 15087) and final rule (82 FR
6278).
HHS/CDC newly proposes to add definitions and provisions to further
clarify inactivation of select agents; adding requirements for
reporting discoveries of select agents and toxins; provisions regarding
effluent decontamination system; and biosafety provisions for facility
verification requirements for registered biosafety level 3 and animal
biosafety level 3 laboratories.
HHS/CDC also newly proposes to remove Brucella abortus, Brucella
melitensis, and Brucella suis from the select agent list; update the
terminology and clarify the specific clade that is a select agent by
changing ``Monkeypox virus'' to ``Mpox virus (clade I)''; and to change
``SARS coronavirus (SARS-CoV)'' to ``Severe acute respiratory syndrome
coronavirus (SARS-CoV)'' to correct the nomenclature; and to remove the
exclusion regarding South American genotype of Eastern Equine
Encephalitis virus as this terminology is no longer the correct
nomenclature. HHS/CDC is interested in comments regarding these
proposed revisions.
In addition, HHS/CDC is proposing to incorporate existing policies
previously published and found at www.selectagents.gov into regulations
and is soliciting public comments on these policies, further discussed
below, regarding roles of the Responsible Official and Alternate
Responsible Official, chemical inactivation of tissues, conclusion of
patient care, annual internal inspections, inactivation certificates,
deviation from a validated inactivation procedure or a viable select
agent removal method, studies involving naturally infected animals,
formalin-fixed paraffin-embedded tissues containing a select agent,
validated inactivation procedures, and in-house validation. This is a
standard practice for HHS/CDC to utilize policy to first refine its
practices before codification. This helps to ensure that regulated
entities are able to implement the requirements. In addition, HHS/CDC
proposes to correct editorial errors. By codifying these existing
policies into regulation, HHS/CDC aims to provide clarity and stability
in program requirements, make compliance more straightforward for
regulated entities, and ensure enforcement is consistent and
predictable across the regulated community.
Specifically, HHS/CDC is seeking comments on whether any of the
proposed changes would create an additional burden in implementing the
proposed changes.
A. Definitions
HHS/CDC is proposing to add or revise the following eight terms to
section 73.1 of the regulations (Definitions) to clarify the use of
these terms in the regulations.
The ``loss,'' ``release,'' and ``theft'' definitions are proposed
to be added to assist the regulated community on what is to be reported
as required under Section 19. The definition of ``discovery'' relates
to the proposed new reporting requirement further discussed below. The
addition of proposed definitions of ``validated removal procedure'' and
``verification viability testing protocol'' and the revisions of
``validated inactivation procedure'' and ``viability testing protocol''
will provide clarity on inactivation provisions outlined in regulations
in Sections 3, 4, 9 and 17. The new terms include:
Discovery means the finding of a select agent or toxin by
an individual or entity that is not aware of the select agent or
toxin's existence. Examples include, but are not limited to, the
following:
(1) A registered individual or entity finds a select agent or toxin
not accounted for in their inventory; or
(2) A non-registered individual or entity finds a select agent or
toxin.
Loss means the inability to account for a select agent or
toxin known to be in the individual's or entity's possession.
Release means any of the following:
(1) an incident resulting in occupational exposure to a select
agent or toxin,
(2) an incident resulting in animal/plant exposure to a select
agent or toxin,
(3) the failure of equipment used to contain a select agent or
toxin such that
[[Page 5826]]
it is reasonably anticipated that a select agent or toxin was released,
(4) the failure of or breach in personal protective equipment in
the presence of a select agents or toxin, or
(5) the failure of biosafety procedures such that it is reasonably
anticipated that a select agent or toxin was outside of containment.
Theft means the unauthorized taking and removing of a
select agent or toxin from the possession of an individual or entity.
Validated removal procedure means a procedure, whose
efficacy has been confirmed by data generated in-house from a viability
testing protocol, to remove all viable select agent, or nucleic acids
of any select agent virus capable of producing infectious virus.
Verification viability testing protocol means a protocol,
used on samples that have been subjected to a validated inactivation or
removal procedure, to confirm the material is free of all viable select
agent, or nucleic acids of any select agent virus capable of producing
infectious virus.
Existing definitions being revised include:
Validated inactivation procedure means a procedure, whose
efficacy has been confirmed by data generated from an in-house
viability testing protocol, to render a select agent non-viable but
allows the select agent to retain characteristics of interest for
future use; or to render any nucleic acids that can produce infectious
forms of any select agent virus non-infectious for future use.
Viability testing protocol means a protocol used to
confirm the efficacy of the inactivation or removal procedure by
demonstrating the material is free of all viable select agent, or
nucleic acids of any select agent virus capable of producing infectious
virus.
B. Removal of Brucella abortus, Brucella melitensis, and Brucella suis
HHS/CDC is proposing removing B. abortus, B. melitensis, and B.
suis from the select agents and toxins list based on a review of
considerations outlined under 42 U.S.C. 262a(a)(1)(B). That provision
calls for consideration of (1) an agent's effect on human health, (2)
degree of contagiousness, (3) the availability and effectiveness of
pharmacotherapies and immunizations, and (4) other appropriate criteria
as determined by the HHS Secretary. With regard to the effect on human
health, Brucella infections have a low case fatality rate, with an
untreated fatality rate usually ranging from 1-2% of those identified
with the infection (Spickler, 2018). Brucellosis typically causes mild
clinical symptoms (flu-like illness) (Olsen et al., 2018). With regard
to the degree of contagiousness, there is no indication that Brucella
is transmitted between people by casual contact under ordinary
conditions. Humans are typically infected from exposure to animal
reservoirs or animal products; transmission to humans from wildlife is
a rare event unless an individual directly handles infected animals,
such as in butchering meat (Godfroid et al., 2013). With regard to the
availability of effective pharmacotherapies, disease caused by these
bacteria is treatable with antibiotics (Spickler, 2018).
In the ANPRM, HHS/CDC sought comments on whether B. abortus, B.
melitensis, and B. suis should be removed or retained on the select
agents and toxins list, with a substantial majority supporting removal
of the agents. HHS/CDC received four comments recommending the
retention of B. abortus, B. melitensis, and B. suis on the list of
select agents and toxins. One commenter indicated that if state public
health laboratories no longer accept specimens suspected as containing
these Brucella species for confirmatory testing, then the burden of
such confirmatory testing will fall upon the sentinel laboratories of
the Laboratory Response Network (LRN). The commenter further argued
that all clinical laboratories do not have the engineering controls
(e.g., biological safety cabinets) needed to perform these procedures
safely and there could be a risk of occupational health and safety
concerns if identification activities are not done with appropriate
care. Regardless of an agent's status on the select agent list,
clinical laboratories will likely continue to be exposed to these
agents when conducting diagnostic procedures or working with unknown
samples if sufficient biosafety and personal protective measures are
not taken. Furthermore, removing an agent from the select agents and
toxins list does not preclude state laboratories from providing
testing; HHS/CDC does not direct the testing provided by these
laboratories. The other commenter agreed with retention because
Brucellosis is a very serious human disease and Brucella spp. are
easily spread in a laboratory environment where laboratory acquired
cases are not rare. Another commenter stated that Brucella species are
known to have a low infectious dose and therefore present an increased
risk of infection due to laboratory exposures. In addition, Brucella is
the top laboratory acquired infection reported by clinical laboratories
to public health laboratories. If removed from the select agent list,
the commenter stated that it is likely that hospitals will no longer
report these exposures, leaving many laboratorians at risk. For these
reasons, the commenter recommended that Brucella should be stringently
regulated and therefore remain as a select agent. While HHS/CDC agrees
with the commenters that Brucella has a low infectious dose, the case
fatality rate and person-to-person transmission for Brucella continues
to be very low. In addition, the human illnesses are readily recognized
and treated.
HHS/CDC received 36 comments that supported removal based on the
considerations provided in the ANPRM and stated that the agents should
be removed so that important research can be conducted to include
vaccine development. Another 286 commenters supported the removal of B.
abortus to reduce the regulatory burden so that effective research can
be conducted towards the development of improved vaccination for
livestock, diagnostics, and other livestock management options. Two
commenters supported the removal of B. abortus and B. suis to reduce
the regulatory burden to further the development of diagnostic testing,
effective vaccines, and further assistance in controlling the agent.
Another commenter believes B. abortus and B. suis to be poor selections
for a biological agent. While B. suis was one of the first bioweapons
developed by the United States in the 1950s, there have been many more
insidious and potent pathogens that have been identified in the past 70
years (Olsen et al., 2018). Although B. abortus and B. suis have
zoonotic capabilities, humans are essentially dead-end hosts for
brucellosis making it improbable that an infected person can transmit
the disease to another person (Olsen et al., 2018). Other disease
characteristics of brucellosis, including mild clinical symptoms, the
long incubation period, positive response to antibiotic/pharmacotherapy
treatment, low risk of human-to-human transmission, and low mortality
rate, further decrease the attractiveness of B. abortus, B. melitensis,
and B. suis as bioweapons (Centers for Disease Control and Prevention,
2017; Cross et al., 2019; Shakir, 2021).
In accordance with the criteria and considerations for determining
whether to include an agent or toxin on the list as articulated in 42
U.S.C. 262a, HHS/CDC is proposing to remove B. abortus, B. melitensis,
and B. suis from the HHS select agents and toxins list. The minimal
effects on human health upon exposure to these agents, the degree of
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contagiousness of these agents, the methods by which these agents are
transferred to humans, and the availability and effectiveness of
pharmacotherapies to treat illness resulting from these agents are key
considerations for this proposal. HHS/CDC would be interested in
comments on this proposal. Please provide a detailed explanation for
your response. Since B. abortus, B. melitensis, and B. suis are overlap
select agents, even if HHS/CDC removes them from its list, these agents
might still be regulated as USDA select agents dependent on the outcome
of USDA biennial review.
C. Botulinum Neurotoxin Producing Species of Clostridium
Botulism is a serious paralytic disease caused by a neurotoxin
produced during the growth of the spore-forming bacterium Clostridium
botulinum (or rarely, C. argentinense (Puig de Centorbi et al., 1997),
C. butyricum, or C. baratii) (Sobel, 2005). In the ANPRM, HHS/CDC
requested comment on whether this agent should be removed or retained
from the select agents and toxins list because the organism does not
normally cause disease. At this time, HHS/CDC is proposing to retain
Botulinum neurotoxin producing species of Clostridium as an HHS select
agent because it produces the highly toxic Botulinum neurotoxin (a
select toxin). Given the risk that the agent can produce such a potent
toxin, HHS/CDC is proposing to retain this organism as an HHS select
agent; however, HHS/CDC is also proposing that because the organism
itself does not normally cause disease, it no longer be listed as a
Tier 1 agent.
HHS/CDC received mixed reactions on whether to retain or remove the
agent. Six comments supported the retention of the agent; however, five
supported the removal. Besides the information included in the ANPRM
for removal, that the organism does not cause disease, one commenter
added that the disease botulism is caused by intoxication with protein
toxins, botulinum neurotoxins, and not by intoxication with C.
botulinum. Therefore, the commenter further explained that human
botulism cases are rare and can be managed with antitoxin treatments.
HHS/CDC received one comment that spores of botulinum neurotoxin
species of Clostridium, used to conduct experimental food challenge
studies, should be excluded from the HHS list of select agents because:
Basic biological safety practices are already sufficient
to protect laboratory personnel and the public.
Inoculated food samples replicate the concentrations of
spores that may be naturally found in the foods or soils or sediments.
Botulinum spores are not infectious to the general public
of healthy individuals older than 1 year of age.
Toxin production for inoculated samples is no greater than
that which may occur naturally if a consumer were to mishandle or
temperature-abuse low acid foods.
HHS/CDC disagreed that experimental food challenge studies should
be excluded from the regulations. Since this work would require
possession and manipulation of the select agent Botulinum neurotoxin
producing species of Clostridium, and is not diagnostic in nature, this
work is not exempted from the select agent and toxin regulations. Cells
or spores of botulinum neurotoxin producing species of Clostridia are
introduced into the samples intentionally. Therefore, this work would
be regulated by the select agent regulations.
Six commenters did not support the removal of botulinum neurotoxin
producing species of Clostridia. One commenter recommended that the
organism not be considered as Tier 1 select agent. Two commenters
argued the bacteria grows and produces toxin relatively easily (Peck,
2009). One commenter further claimed that normally the bacterium exists
in the environment as a dormant spore; however, in environments such as
in canned foods, deep wounds, or the intestinal tract, the spores
germinate into vegetative bacteria. Two commenters stated that with
access to these strains, a simplistic grocery-grade broth filled to the
maximum volume or neck of a container is enough for the criminals to
drive the fermentation process following inoculation of such strains.
Another commenter argued that a botulism outbreak, whether natural or
deliberate, can quickly overwhelm local health care systems. Commenters
further disagreed with the comparison of the organism to S. aureus not
being regulated, but that its toxins are because the commenters stated
that Staphylococcal enterotoxins are not nearly as potent and fatal as
botulinum neurotoxin. The other commenter disagreed because in order to
produce the purified botulinum neurotoxins that are used in medicine,
food safety, and other fields, the commenter argued that it is
essential to secure strains or recombinant organisms of neurotoxigenic
Clostridia for consistent production of high-quality botulinum
neurotoxins (i.e., those strains that produce true toxins). Another
commenter argued that a terrorist could use the crude toxin cell
extracts and not purified toxin for weaponization purposes. Two
commenters stated that the removal of the agent status could set a
wrong precedence for recombinant strains to express biologically active
toxin for easy and bulk production. A commenter also indicated that
medical clinicians often use highly purified toxins, but these still
need to be made by neurotoxigenic organisms including special strains.
As the toxin produced by these species remains regulated, a commenter
stated that the agent should be retained since it is not currently
standard practice for public health laboratories to quantify toxin
levels following identification of C. botulinum. If the agent is
retained as an HHS select agent, two commenters requested that changes
be made to the regulations to: (i) relax the current inventory format
of maintaining stocks or working stocks; (ii) relax or remove in-house
validation and verification requirements (to test 10% volume or sample
size subjected to agent inactivation and/or removal procedures), while
implementation of a terminal filtration step to remove the cells or
spore forms from the research or analytical samples needs to be
continued to ensure the security of the agent; and (iii) include more
waiver provisions for bona fide research as needed, or on a case by
case basis (e.g., food challenge studies, countermeasure development,
emergencies, proficiency testing and diagnostics etc.). HHS/CDC
disagreed with the commenters that certain provisions should be
relaxed. If an individual or entity is registered to possess, use, or
transfer a select agent, then the individual or entity is required to
meet all the regulatory requirements for the select agent. It should be
noted that the current regulations do not contain provisions regarding
``working stocks'' and contain a provision for an individual or entity
to obtain a waiver for ``a select agent or regulated nucleic acids that
can produce infectious forms of any select agent virus not subjected to
a validated inactivation procedure or material containing a select
agent not subjected to a procedure that removes all viable select agent
cells, spores, or virus particles if the material is determined by the
HHS Secretary to be effectively inactivated or effectively free of
select agent'' (See 73.3 (d)(6)).
In accordance with the criteria and considerations for determining
whether to include an agent or toxin on the list articulated in 42
U.S.C. 262a, HHS/CDC agreed with the six commenters to retain botulinum
neurotoxin producing species of Clostridia as an HHS select
[[Page 5828]]
agent. HHS/CDC made the determination because the toxin is easily
secreted by botulinum neurotoxin producing species of Clostridia which
makes it simple to isolate the lethal toxin.
HHS/CDC also agreed and has determined that the botulinum
neurotoxin producing species of Clostridia should no longer be
identified as a Tier 1 select agent. Tier 1 select agents and toxins
pose a severe threat to public health and safety and are considered to
present the greatest risk of deliberate misuse with significant
potential for mass casualties or devastating effect to the economy,
critical infrastructure, or public confidence. Because the organism
itself does not meet this definition and does not normally cause
widespread disease, HHS/CDC does not believe the organism should be
designated as a Tier 1 select agent. HHS/CDC would continue to retain
Botulinum neurotoxins as a Tier 1 agent. HHS/CDC would be interested in
comments on retaining botulinum neurotoxin producing species of
Clostridia as an HHS select agent and not as a Tier 1 select agent.
Please provide a detailed explanation for your response.
D. Hantaviruses
In the 2020 ANPRM, HHS/CDC requested public comment on whether Sin
Nombre virus (SNV), Andes virus (ANDV), Hantaan virus (HTNV), and
Dobrava virus (DOBV) should be considered HHS select agents given the
fatality rate and low infectious/lethal doses of these viruses. Based
on a review of considerations outlined under 42 U.S.C. 262a(a)(1)(B)
and the public comments submitted by subject matter experts, HHS/CDC is
not proposing to add these viruses to the select agent list.
Specifically, the very limited direct person-to-person transmission of
hantaviruses, the difficulty of propagating the organisms in a
laboratory setting, and the fact that the infectious dose of hantavirus
for humans is higher than the doses provided in ANPRM indicate that
these viruses are not appropriate for inclusion on the select agent
list.
HHS/CDC received one comment that supported this addition of the
viruses as HHS select agents. HHS/CDC received three comments that did
not support the addition of these viruses as HHS select agents. The
commenters who did not support listing argued that adding these viruses
will result in a significant burden on research institutions. For those
institutions that already have a select agent program and registered
laboratories established, one commenter argued adding new agents may
crowd existing laboratory spaces and will likely result in slowed
research and development of vaccines and treatments for all agents
studied within the space. The commenter further explained that new
requirements would take considerable time, delay critical research
programs, and require increased funding. Two commenters presented the
following reasons to not include these viruses as select agents:
Current laboratory practices and biosafety regulations do
not expose research personnel and the larger community to high risk of
hantavirus infection (e.g., direct person-to-person transmission of
hantaviruses has not been documented for any hantavirus, except for
very limited confirmed events for Andes virus in South America;
laboratory-acquired infections have not been documented for these
viruses since the adoption of ABSL-3 (HTNV, DOBV) and ABSL-4 (SNV,
ANDV) practices; and lack of approved therapeutics and vaccines is not
sufficient criteria for select agent inclusion based on other emerging
RNA virus classifications (such as West Nile virus, Zika virus,
Powassan virus, many non-endemic Influenza A viruses, chikungunya
virus).
The infectious dose of any hantavirus for humans is likely
much higher than those presented in the proposal, as evidenced by non-
human primate studies and strikingly rare infections despite endemicity
in rodent reservoirs and significant ecological overlap between humans
and reservoirs.
These viruses do not pose a national security threat as
potential bioweapons due to the notoriously challenging culture
conditions of even laboratory-adapted strains and the scarcity of
tractable animal models or amplifying hosts.
This designation of select agent status will significantly
disrupt ongoing research operations.
HHS/CDC agreed with two commenters and has decided not to propose
adding these Hantaviruses as HHS select agents. As explained above,
there has been very limited direct person-to-person transmission. In
addition, the infectious dose for humans is likely higher than the
doses provided in ANPRM, and it is difficult to propagate in a
laboratory setting. HHS/CDC would be interested in comments on adding
these Hantaviruses as HHS select agents. Please provide a detailed
explanation for your response.
E. Toxin Review: Changes to Exclusion Limits for Short, Paralytic Alpha
Conotoxins
HHS/CDC is proposing to increase the exclusion amount for short,
paralytic alpha conotoxins from 100mg to 200mg based on assessments of
lethal doses of conotoxin compared to other regulated toxins and the
amount of the toxin that would be needed if a bad actor sought to
weaponize it.
In the 2020 ANPRM (85 FR 15087), HHS/CDC requested comments on
whether any toxins should be retained, removed, or if the exclusion
amount for each toxin should be increased or decreased. Specifically,
HHS/CDC requested comments for short, paralytic alpha conotoxins
containing the following amino acid sequence
X1CCX2PACGX3X4X5X
6CX7. Alpha conotoxins are low, molecular weight
toxins that are isolated from the venom bulb of the marine cone snail.
These toxins present a public health threat because they are highly
toxic, more stable, and can persist for longer periods of time in the
environment. Additional toxins requested for public comment include
Diacetoxyscirpenol and Staphylococcal enterotoxins.
One commenter agreed with the proposal to remove short, paralytic
alpha conotoxins and diacetoxyscirpenol. However, the commenter did not
provide any rationale to why these toxins should be removed. The same
commenter did not support the removal of Staphylococcal enterotoxins
because the toxins, while rarely fatal, cause severe cases of food
poisoning. Furthermore, the commenter stated that the toxins have been
explored as a potential biological weapon during the cold war. In the
1960's, three different occurrences of laboratory exposure were
reported, and the pathogenic dose is extremely low (Pinchuk et al.,
2010). The commenter argued that the isolation of Staphylococcal
enterotoxins is relatively easy and would make for a nearly untraceable
method of bioterrorism as illnesses would most likely be treated as
food poisoning due to the mishandling of food. HHS/CDC agreed with the
commenter that Staphylococcal enterotoxins should remain as a select
toxin because the enterotoxins can cause severe food poisoning and, in
rare cases, can be fatal. Since no rationale was provided to remove
diacetoxyscirpenol as a select toxin, HHS/CDC has decided it should be
retained as an HHS select toxin.
In response to the Notice of Proposed Rulemaking (81 FR 2805), one
commenter supported the removal of
[[Page 5829]]
short paralytic alpha-conotoxin and one comment opposed the removal of
short paralytic alpha-conotoxin. The commenter that opposed removal
stated that: (1) the LD50 (lethal dose, 50% or median lethal
dose, the amount of the substance required (usually per body weight) to
kill 50% of the test population) of 20 [mu]g/kg for the short paralytic
alpha-conotoxin is not a low toxicity compared to other select agents,
and this LD50 is actually in line with other marine toxins
included on the list, such as Tetrodotoxin and Saxitoxin; (2) the
LD50 of actual cone snail venom may be lower due to the
synergistic effect of multiple conotoxins; and (3) conotoxins can be
readily synthesized. The commenter further asserted when using solid
phase peptide synthesis, ten grams of toxin is not difficult to
produce. HHS/CDC agreed with the commenter and determined that
conotoxins (short, paralytic alpha conotoxins containing the following
amino acid sequence
X1CCX2PACGX3X4X5X
6CX7) should be retained as an HHS select toxin
because the ability to produce the toxin synthetically is easier now
with more modern technology.
While HHS/CDC did not receive any comments regarding whether the
exclusion amount for each toxin should be increased or decreased,
likely due to insufficient evidence on LD50 levels in humans
through various routes of intoxication, HHS/CDC is not proposing any
changes to the current exclusion limits for the toxins, with the
exception of short, paralytic alpha conotoxins. To assess the amount
necessary to weaponize a biological toxin, the Department of Homeland
Security (DHS) developed toxin parameters and attack scenarios for
potential inhalation and ingestion exposures to select toxins. The DHS
models determined the impact of the dissemination of varying
concentrations of toxin on public health. HHS/CDC believes the amount
of each toxin, with the exception of conotoxins, that could be
possessed without regulation by a principal investigator, a treating
physician or veterinarian, or a commercial manufacturer or distributor
was determined on the basis of toxin potency and how much one could
safely possess without constituting a potential threat to public safety
or raising concerns about use as a weapon that would have a widespread
effect. HHS/CDC reviewed the LD50 used for the calculations
and the ingestion/inhalation scenarios, and the lethal doses of
conotoxins are comparable to other regulated toxins with a much higher
permissible amount. Therefore, HHS/CDC believes that the exclusion
limit can be increased and still not pose a severe threat to public
health. In 2017, HHS/CDC inadvertently did not propose an increase in
the exclusion limit for short, paralytic alpha conotoxins in the Notice
of Proposed Rulemaking (81 FR 2805). Based on the DHS model, HHS/CDC
proposes to raise the exclusion limit for conotoxin from 100 mg to 200
mg based on the toxin parameters and attack scenarios for potential
inhalation and ingestion exposures to this select toxin. HHS/CDC would
be interested in any comments regarding raising the exclusion limit
from 100 mg to 200 mg. Please provide a detailed explanation for your
response.
F. Renaming Ebola Virus to the Genus Ebolavirus
Recently, the International Committee on Taxonomy of Viruses (ICTV)
published a report on the virus family Filoviridae, which classified
the species of Ebola and Ebola-like viruses that are in the genus
Ebolavirus (Kuhn et al., 2019). To date, there are six species in the
genus Ebolavirus, including Ebola virus, Bombali virus, Reston virus,
Bundibugyo virus, Sudan virus, and Ta[iuml] Forest virus. Currently,
the HHS/CDC select agent list includes the name Ebola virus to
encompass all of the six viruses listed above in the genus Ebolavirus.
HHS/CDC is seeking public comment on whether Ebola virus, on the HHS/
CDC select agent list as a Tier 1 select agent, should be renamed as
Ebolavirus to agree with the recent taxonomic change by ICTV. Please
provide a detailed explanation for your response.
G. Designating Nipah Virus as a Tier 1 Select Agent
Executive Order 13546 ``Optimizing the Security of Biological
Select Agents and Toxins in the United States'' directed the HHS
Secretary to designate a subset of select agents and toxins that
present the greatest risk of deliberate misuse with the most
significant potential for mass casualties or devastating effects to the
economy, critical infrastructure, or public confidence. This subset of
select agents and toxins is identified as Tier 1. In the ANPRM, HHS/CDC
sought public comment on whether Nipah virus should be identified as a
Tier 1 select agent because the public health threat posed by Nipah
virus is similar to that of Marburg and Ebola viruses, in terms of
human transmissibility and high case fatality rate, which are both
currently Tier 1 agents. It was also noted in the ANPRM that entities
that are currently registered to possess Nipah virus are also in
possession of other Tier 1 select agents. HHS/CDC received only one
comment in support of this proposal. HHS/CDC is proposing Nipah virus
should be identified as a Tier 1 select agent because of its:
Human transmissibility (person-to-person transmission has
occurred) (Centers for Disease Control and Prevention, 2014; Gurley et
al., 2007; Luby et al., 2012; and Luby et al., 2009).
High case fatality rate (estimated between 40-100%) (World
Health Organization, 2017 and Harcourt et al., 2004).
Low infectious dose (ranging from 10\1\-10\7\ plaque
forming units depending on route of infection) (DeWit et al., 2014;
Geisbert et al., 2010; and Mathieu et al., 2012).
High severity of illness, including fever, headache,
dizziness, vomiting, cough, reduced levels of consciousness,
respiratory distress, and in some cases, death (Hossain et al., 2008;
and Lo et al., 2008).
Severe long-term effects, including neurological
complications including encephalopathy, cranial nerve palsies, and
dystonia (Sejvar et al., 2007 and Lo et al., 2008). These complications
and long-term side effects in survivors of Nipah virus infection can
also include persistent convulsions and personality changes.
HHS/CDC would be interested in comments on this proposal. Please
provide a detailed explanation for your response.
[[Page 5830]]
H. Adding a Footnote to the HHS Select Agent List
For viruses, the International Committee on Taxonomy of Viruses
(ICTV) is the international group that sets the standards for names of
viruses. Commonly accepted names are still used in the virus community,
but there is an effort to create a standard nomenclature. The
committees are made up of virus specialists around the world (including
from HHS/CDC specialists) to standardize nomenclature and work to avoid
confusion. HHS/CDC is working to harmonize list of select agent viruses
with ICTV to match the international standard. However, we want to
ensure that the common names are also reflected (or at least captured)
so if a name changes or is modified, then the list of select agent
viruses is still accurate. As such, HHS/CDC proposes to add a footnote
to the list for HHS select agents indicating that the current
nomenclature will be available on the FSAP website (https://www.selectagents.gov).
I. Discovery of Select Agents or Toxins
Since the implementation of the select agent and toxin regulations
in 2003 (HHS/CDC, 2003), unless a regulatory exemption or exclusion is
applied, individuals and entities are required to register with HHS or
USDA to possess a select agent or toxin. Possession of regulated
material without proper registration is a regulatory violation that
could result in civil, criminal, and/or administrative penalties. Since
this time, there have been at least 100 instances of reports from
entities that ``discovered'' a select agent or toxin in their
possession that the individual or entity was neither registered to
possess as required. Many of the agents and toxins ``discovered'' were
from studies associated with personnel who had left their entity, and
the custodianship of samples was not reassigned. Some of the materials
were labeled with obsolete pathogen names, while other ``discovered''
material were found in laboratories where their active use had ceased,
in some cases, decades prior to the establishment of the select agent
and toxin regulations.
HHS/CDC continues to receive reports from entities who find
themselves in possession of select agents and toxins that they are not
registered to possess. Given these instances, HHS/CDC is proposing to
amend section 73.2 of the regulations to clearly state that any
individual or entity in possession of a select agent or toxin, for
which (1) an exclusion or exemption listed in 42 CFR part 73 does not
apply, and (2) that is not included on a certificate of registration
issued by the HHS Secretary or USDA Administrator for that individual
or entity, must immediately report such possession to either the HHS
Secretary or USDA Administrator. This proposal ensures that all
discoveries of possession of a select agent or toxin is reported using
the proposed new form regardless of if the individual or entity is
registered with the program. As such, registered entities that
knowingly come into possession of a material prior to amending their
registration would report the possession using the proposed form. HHS/
CDC would be interested in comments regarding the proposal to ensure
the reporting of discovered select agents and toxins including if there
is an undue burden being placed on registered entities to report the
discovery as well as amending their registration.
To facilitate such reporting, HHS and USDA plan to create, in
compliance with the Paperwork Reduction Act, a new APHIS/CDC Form 6 to
specify the information that must be submitted regarding the discovery
of the select agent or toxin. Establishing a standard form for
reporting will enable HHS and USDA to better understand the
circumstances and assess regulatory violations related to the
possession of ``discovered'' select agents and toxins.
J. Non-Possession of Select Agent or Toxin by a Registered Entity
HHS/CDC is proposing to clarify throughout the regulations that
whenever an individual or entity is registered to possess, use or
transfer a select agent or toxin, the individual or entity is required
to meet all of the regulatory requirements for those select agents and
toxins listed on the individual or entity's certificate of registration
regardless of whether the select agent or toxin is in the actual
possession of the individual or entity and without regard to the amount
of toxin possessed. Registration permits an individual or entity to
possess select agents and toxins at any time and indicates its
readiness to do so.
K. The Electronic Federal Select Agent Program (eFSAP) Information
System
HHS/CDC utilizes a highly secure information system, the eFSAP
information system, to conduct all select agent program activities. The
eFSAP information system is a two-way communication portal, which is
accessible by both CDC and APHIS staff and the regulated community. For
users at registered entities, benefits of the system include reduced
paperwork, increased ease of validating and submitting information, and
reduced processing time for requests (as real-time information exchange
allows for increased responsiveness). Based on the implementation of
the eFSAP information system, HHS/CDC is proposing to update provisions
to indicate that reports (e.g., APHIS/CDC Forms 2, 3, and 4) and
requests (e.g., amendments to registration) can be submitted via the
eFSAP information system (or successor IT system as specified by CDC in
guidance). In addition, the electronic documentation in the eFSAP
information system serves as official records required by the select
agent and toxin regulations, and once submitted in the eFSAP
information system, there is no requirement for entities to retain a
separate copy.
L. Registration
The certificate of registration is the document issued by the
Federal Select Agent Program to an individual or entity that denotes
approval to possess, use and/or transfer specified select agents and
toxins; the specific activities related to the registered select agents
and/or toxins; persons authorized to access the select agents and/or
toxins; and the locations (buildings, rooms, suites of rooms, storage
facilities, etc.) where select agents and/or toxins are authorized to
be present as described in the individual or entity's APHIS/CDC Form 1.
The issuance of a certificate of registration may be contingent upon
inspection or submission of additional information, such as the
security plan, biosafety plan, incident response plan, or any other
documents required to be prepared to meet requirements of the select
agent and toxin regulations. In addition, the certificate of
registration is required to be amended prior to making any changes and
must be reauthorized at least every three years from the date it was
initially issued or renewed. The individual or entity's certificate of
registration must be amended to reflect changes in circumstances
relative to the possession and use of select agent and toxins (e.g.,
replacement of the Responsible Official or other personnel changes,
changes in ownership or control of the individual or entity, changes in
the locations and activities involving any select agents or toxins, or
the addition or removal of select agents or toxins). As such, HHS/CDC
is proposing clarification to language to explain that an amendment
``must'' be submitted instead of ``may'' for any changes to the
approved certificate of registration. The proposal corrects a
discrepancy between language found in (i) that states an amendment may
be
[[Page 5831]]
submitted versus language found in (i)(1), which states that the
Responsible Official must apply for amendment. An entity must submit an
amendment prior to making any change. Therefore, the use of ``may'' is
not an accurate term. With the use of eFSAP information system instead
of the submission of a revised form, HHS/CDC proposes to update
language to replace ``additional documents'' to ``additional
information'' since information is what is being revised in the system
and not documents.
M. Tier 1 Security Enhancements
HHS/CDC is proposing to clarify security enhancements regarding
screening visitors for those entities possessing Tier 1 select agents
and toxins because HHS/CDC believes the new language clearly specifies
the requirements and will aid in compliance. The proposed provision has
been revised to read: ``Entities with Tier 1 select agents and toxins
must prescribe the following security enhancements: Procedures for
screening visitors, their property, and, where appropriate, vehicles at
entry and exit points to registered space based on the entity's site-
specific risk assessment.'' While HHS/CDC does not have any evidence of
non-compliance, HHS/CDC has received feedback from the registered
entities requesting clarification on the current provision that reads:
``Procedures for allowing visitors, their property, and vehicles at the
entry and exit points to the registered space, or at other designated
points of entry to the building, facility, or compound that are based
on the entity's site-specific risk assessment.'' HHS/CDC believes the
proposed provision will clarify there are multiple checkpoints needed
to ensure compliance with the Tier 1 requirement.
N. Biosafety--Facility Verification
HHS/CDC is proposing to require facility verification every 12
months for registered entities that maintain biosafety level 3 and
animal biosafety level 3 laboratories. The proposal is to codify the
2014 policy that provided specific provisions for the verifications
regarding BSL-3/ABSL-3 facilities to meet the requirements outlined
under 42 CFR 73.12(b) ``biosafety and containment procedures must be
sufficient to contain the select agent or toxin (e.g., physical
structure and features of the entity, and operational and procedural
safeguards).'' The verifications also must be documented and validate
the facility's containment functions such as inward directional
airflow, decontamination systems, and preventative maintenance.
Therefore, HHS/CDC is proposing to require the entity to document
facility verification and require the entity to verify the facility's
containment functions.
HHS/CDC does not believe that the new provisions will create an
additional burden to entities that maintain biosafety level 3 and
animal biosafety level 3 laboratories since these entities are already
performing annual facility verifications. However, if a registered
entity has not been performing annual facility verifications for
biosafety level 3 and animal biosafety level 3 laboratories, HHS/CDC
would be interested in comments concerning the cost and burden of
annual facility verifications, especially if the entity is considered a
small business.
O. Biosafety--Effluent Decontamination System
Biosafety level 3 and biosafety level 4 facilities are highly
sophisticated facilities built to contain biological agents and toxins
with the highest potential to threaten agricultural, plant and public
health and safety. Any defect, such as a crack or leaky pipe, could
have severe consequences. In August 2007, foot-and-mouth disease was
discovered at farms in the United Kingdom. The source of the
contamination was determined to be long-term damage and leakage of a
drainage system used by a high-containment laboratory working with the
foot-and-mouth disease virus. Given these risks, HHS/CDC is proposing
to amend the security, biosafety, and incident response sections of the
select agents and toxins regulations to address risks posed by the
effluent decontamination systems used by biosafety level 3 and
biosafety level 4 facilities.
If an effluent decontamination system is used by an entity, the
entity must include in its plans how it will address security,
biosafety, and incident response as it relates to the system.
Specifically, the biosafety plan must provide for verification that the
liquid waste generated from registered space is sufficiently treated to
prevent the release of a select agent or toxin prior to discharge of
the waste from the facility. The security plan, for any space not
listed on the entity's registration that contains a portion of an
effluent decontamination system, must describe procedures to prevent
the theft, loss, or unauthorized access to a select agent or toxin. The
incident response plan must fully describe the entity's response
procedures for the theft, loss, or release of a select agent or toxin;
the failure of an effluent decontamination system resulting in a
release of a select agent or toxin, and how personnel will access an
area potentially containing a select agent or toxin due to the failure
of an effluent decontamination system.
P. Restricted Experiments
HHS/CDC proposes to clarify the provision that the receiving entity
must amend their certificate of registration and receive approval by
CDC or APHIS to possess the products of a restricted experiment.
Entities are currently required to obtain approval to conduct
restricted experiments and possess the product of a select agent or
toxin that results from a restricted experiment. However, the current
provisions do not address if the entity comes into possession of a
product of a restricted experiment based on the transfer of the agent.
This proposal aligns with the registration section where the
Responsible Official must apply for an amendment and receive approval
prior to any change in the registration, such as the receipt of a
product of a restricted experiment. The proposed provisions also ensure
receiving entities have the appropriate safeguards in place to receive
and possess the product from a transfer.
Q. Training
HHS/CDC is proposing revisions to the training requirements in
accordance with the new mandate in the Prepare for and Respond to
Existing Viruses, Emerging New Threats, and Pandemics Act (42 U.S.C.
262a(k)(1); Pub. L. 117-328). These revisions have been made in an
effort to comply with the statutory amendment that states training
requirements for (1) unapproved individuals whose responsibilities
routinely place them in close proximity to laboratory facilities and
(2) those individuals who perform administrative or oversight
functions. Trainings must be completed within 6 months after the final
rule is published.
R. Records
HHS/CDC proposes to clarify the records provisions to ensure
accurate, current inventory is maintained for each select agent held in
long-term storage and all toxins to more clearly specify the
requirements and aid in compliance. HHS/CDC is proposing that records
contain: (1) the quantity acquired and the name of the individual by
whom the select agent or toxin was acquired; (2) the location where it
is stored (e.g., building, room number or name, and freezer
identification or other storage container); (3) for removal and return
of the select agent or toxin from storage, the date the select agent or
toxin was
[[Page 5832]]
removed and returned, the purpose for using it, the name of the
individual who removed and returned it, and when applicable, date of
final disposition of the select agent or toxin and by whom; and (4) for
intra-entity transfers (sender and the recipient are covered by the
same certificate of registration), name of the select agent or toxin,
the date of the transfer, the number of items or quantity of the select
agent or toxin transferred, the name of the sender, and the name of the
recipient. HHS/CDC believes the proposed provision will clarify
information needed to ensure the inventory is accurate and complete
from the select agents and toxins origination to destruction. Due to
prior inquiries received from the regulated community, HHS/CDC is
seeking comments on whether the proposed changes are specific enough to
ensure proper records are maintained.
S. Codifying Existing Policies
HHS/CDC is proposing to incorporate five existing policies
previously published and found at www.selectagents.gov into regulations
and are soliciting public comments on these policies, further discussed
below. By codifying these existing policies into regulation, HHS/CDC
aims to provide clarity and stability in program requirements, make
compliance more straight-forward for regulated entities, and ensure
enforcement is consistent and predictable across the regulated
community.
1. Conclusion of Patient Care
HHS/CDC proposes to codify in regulation the current policy that
for an individual who has been admitted to a medical facility, the
``conclusion of patient care'' and the point when ``delivery of patient
(i.e., human) care by heath care professionals has concluded'' is when
an individual is no longer receiving treatment provided by the medical
facility or physician. If the patient is seen by the physician or
medical facility for follow-up care (e.g., six-month follow-up visit),
this would be considered a new delivery of patient care.
The policy also clarified that select agent waste generated during
the delivery of patient care applies only to the treatment of humans.
Accordingly, specimens or waste associated with that individual (e.g.,
tissue samples, body fluids, fomites and any other contaminated
material likely to transmit an infection to people through the
environment if it is unable to be decontaminated) must be destroyed or
transferred to a registered individual or entity within seven days
after an individual is no longer receiving treatment provided by the
medical facility.
2. When Animals Naturally Infected With Select Agents Are Excluded
HHS/CDC proposes to codify in regulation the current policy
regarding when animals naturally infected with select agents are
excluded from the requirements of the regulations. Sections 73.3(d)(1)
and 73.4(d)(1) provide for exclusion of select agents occurring in
their natural environment. Mere possession of an animal that is
naturally infected with a select agent, either within its natural
environment or having been transported to an artificially established
environment, meets the criteria of this exclusion. However, the removal
of an animal which is naturally infected with a select agent from its
natural environment to an artificially established environment for the
purpose of
(1) the intentional exposure or introduction of a select agent to a
na[iuml]ve or experimental animal; or
(2) the introduction of a na[iuml]ve animal to a natural
environment where there is an animal that is naturally infected with a
select agent for the purpose of the intentional exposure or
introduction of a select agent to the na[iuml]ve or experimental
animal, does not meet the exclusion criteria.
If an animal is confirmed to be naturally infected with a select
agent, there may be additional transfer and/or transport restrictions
based upon other federal or state requirements.
3. Inactivation
HHS/CDC proposes to codify into regulation the current policies
regarding inactivation, clarifying and reorganizing the existing
provisions regarding select agent inactivation and select agent
removal, and clarifying that a certificate must be generated prior to
excluding inactivated or select agent-free material.
For chemical inactivation of whole tissue or homogenized tissue,
two options are acceptable when choosing appropriate tissue for
procedure validation. The first option is to use the tissue that is
expected to have the highest concentration of the specific agent to
serve as a surrogate for other tissues, including those in other animal
models, so long as all standardized conditions (e.g., the agent used,
tissue volume, and ratio of tissue to volume of inactivating chemical)
are held constant. The second option is to determine the agent
concentration in a tissue before performing the inactivation procedure
and set this concentration as the maximum agent limit for subsequent
inactivation procedures. A safety margin must be incorporated into the
final chemical inactivation procedure to ensure the effective
inactivation of the agent.
Any select agent or regulated nucleic acid that can produce
infectious forms of any select agent virus is excluded if the material
is contained in a formalin-fixed paraffin-embedded tissue or fixed to
slides (e.g., Gram stain) that have been effectively inactivated by a
recognized method for that particular agent or regulated nucleic acid.
HHS/CDC also proposes to codify the policy that allows individuals
approved by HHS or USDA to access select agents and toxins besides the
Responsible Official (e.g., Principal Investigators) to revise the
inactivation procedures, if necessary. Principal investigator is
defined in the regulations as the one individual who is designated by
the entity to direct a project or program and who is responsible to the
entity for the scientific and technical direction of that project or
program. When a Principal investigator is unavailable (such as out of
the office) to review the results of a select agent that has been
subjected to a validated inactivation or removal procedure, a temporary
designee (appointed by the principal investigator and approved of by
the responsible official) may sign the inactivation certificate to
allow for work to continue. The temporary designee must be listed on
the entity's registration and have the knowledge and expertise to
provide scientific and technical direction regarding the validated
inactivation procedure or the procedure for removal of viable select
agent to which the certificate refers. The appointment of a designee to
sign certificates is not for regular substitution of the principal
investigator, such as the principal investigator relinquishing this
requirement to other individuals in the laboratory due to normal work
demands or general unavailability. In addition, HHS/CDC is proposing to
codify in regulation the current policies regarding records for
inactivated or select agent-free material, to clarify what records are
needed for inactivated or select agent-free material (to include
allowance of a knowledgeable designee to sign the certificate of
inactivation on behalf of a Principal Investigator during his/her
absence, a timeframe after inactivation or select agent removal for
when certificates must be signed and for how long they must be kept by
the entity), and a requirement that certificates accompany all
transfers including intra-entity transfers. These proposed provisions
clarify the recordkeeping
[[Page 5833]]
requirements regarding inactivation procedures and inactivated or
select agent-free material. It also allows Principal Investigators to
designate individuals to sign on their behalf within seven days after
completion of the validated inactivation or validated viable select
agent removal, and require a certificate to be maintained for as long
as the material is in the possession of the registered individual or
entity plus an additional 3 years. The inclusion of the policies into
the regulations verifies the material has been inactivated by the
subject matter expert and the verification document is available
throughout its possession by the entity.
4. Responsible Official and Alternate Responsible Official
HHS/CDC proposes to codify in regulation the current policy that
the Responsible Official (RO) cannot be approved as RO at more than one
registered individual or entity. We also propose to clarify the policy
that a RO cannot be approved to be the sole Alternate Responsible
Official (ARO) at another registered individual or entity. This means
that the RO can serve as ARO at another registered individual or entity
as long as they are not the only ARO at the other individual or entity.
In addition, HHS/CDC proposes to codify in regulation that an
individual who has been approved as an ARO at one individual or entity
can be approved to be an ARO at another registered individual or
entity. The 2017 policy statement regarding Approval of a person to be
a Responsible Official at only one entity, was necessary and was based
on the federal regulations that specify that the RO must ``have a
physical (and not merely a telephonic or audio/visual) presence at the
registered entity to ensure that the entity is in compliance with the
select agent regulations and be able to respond in a timely manner to
onsite incidents involving select agents and toxins in accordance with
the entity's incident response plan.''
5. Annual Internal Inspections
HHS/CDC proposes to codify in regulation the current policy that an
individual or entity's annual internal inspections must address
whether:
1. The individual or entity's biosafety/biocontainment plan is
being effectively implemented, as outlined in Section 12.
2. The individual or entity's security plan is being effectively
implemented, as outlined in Section 11.
3. The individual or entity's incident response plan is implemented
to ensure whether the entity is able to respond, as outlined in Section
14.
4. Each individual with access approval from the HHS Secretary or
Administrator has received the appropriate training as outlined in
Section 15.
The proposal codified the 2019 policy that clarified the language
of section 9 (a) based on the HHS' Office of Inspector General's
Report, ``Entities Generally Met Federal Select Agent Program Internal
Inspection Requirements But CDC Could Do More To Improve
Effectiveness'' (OEI-04-15-00431) recommendation ``to clarify to DSAT
inspectors and to entities the breadth and depth required for internal
inspections, including which of the regulatory sections and subsections
of 42 CFR part 73 must be addressed as inspection standards.''
IV. Alternatives Considered
One alternative to the proposed rule considered by HHS was not to
propose to codify the current operational policies listed above and to
propose the delisting of the select agents. However, we decided to
propose codification for the sake of consistency with USDA and
transparency with our stakeholders. The proposed changes are currently
operationalized, and codification of the policies has been recommended
by various governmental entities. Without codification we would not
have transparency and consistency throughout agencies which is
important when requiring strict adherence to our proposed regulatory
policies for select agents; thus, we have rejected the alternative to
not codify our operational policies that are closely coordinated
between USDA and HHS. Moving forward with codifying the current
operational policies listed above and not proposing to delist the
select agents through federal notice would not be meeting the
regulatory mandate under 42 U.S.C. 262a(a)(2) where the HHS Secretary
must review and republish the list of HHS select agents and toxins at
least biennially.
V. Required Regulatory Analyses
A. Executive Orders 12866, 13563, and 14094
HHS/CDC has examined the impacts of the NPRM under Executive Order
12866, Regulatory Planning and Review (58 FR 51735, October 4, 1993)
and Executive Order 13563, Improving Regulation and Regulatory Review,
(76 FR 3821, January 21, 2011). Both Executive Orders direct agencies
to evaluate any rule prior to promulgation to determine the regulatory
impact in terms of costs and benefits to United States populations and
businesses. Further, together, the two Executive Orders set the
following requirements: quantify costs and benefits where the new
regulation creates a change in current practice; qualitatively describe
costs and benefits; choose approaches that maximize net benefits; and
support regulations that protect public health and safety. HHS/CDC has
analyzed the NPRM as required by these Executive Orders and has
determined that it is consistent with the principles set forth in the
Executive Orders and the Regulatory Flexibility Act, as amended by the
Small Business Regulatory Enforcement Fairness Act (SBREFA).
Executive Order 12866, as reaffirmed by E.O. 13563 and E.O. 14094,
provides that the Office of Information and Regulatory Affairs (OIRA)
in the Office of Management and Budget will review all significant
rules. OIRA has determined that this rule is significant.
Executive Order 14094 reaffirms the principles of E.O. 12866 and
E.O. 13563 and states that regulatory analysis should facilitate agency
efforts to develop regulations that serve the public interest, advance
statutory objectives, and are consistent with E.O. 12866, E.O. 13563,
and the Presidential Memorandum of January 20, 2021 (Modernizing
Regulatory Review). Regulatory analysis, as practicable and
appropriate, shall recognize distributive impacts and equity, to the
extent permitted by law. We have developed this proposed rule in a
manner consistent with these requirements. E.O. 13563 emphasizes
further that regulations must be based on the best available science
and that the rulemaking process must allow for public participation and
an open exchange of ideas. We have developed this proposed rule in a
manner consistent with these requirements. In administering the Federal
Select Agent Program (FSAP), HHS, along with USDA, regularly interact
with the affected registered entities via email, phone, online
webinars, and interactions through the eFSAP information system and
through registered entity designated points of contact. All proposed
changes are being proposed as a direct result of entity questions
received and/or interaction with registered entities who have contacted
FSAP when they had questions or regulatory interpretation requests.
Therefore, HHS/CDC believes this proposed rule serves the public
interest. Additionally, HHS/CDC further encourages public participation
and will inform registered entities of this proposed rule via a Select
Agent (SA) Gram to ensure they are aware that they have a chance to
provide public
[[Page 5834]]
comments. The proposed rule will also be communicated to the general
public via a GovD message to ensure the public has a chance to review
and provide comments. The Federal Select Agent Program website
(www.selectagents.gov) will also be updated to share what the proposed
changes are and will provide a link to web visitors so that they can
review and provide comments on our Federal Register notice. Lastly,
outreach notes summarizing the proposed rule will be emailed directly
to national partner organizations (The Association of Public Health
Laboratories, American Society for Microbiology, American Biological
Safety Association, etc.) so that they can share among their
constituents.
We have prepared an economic analysis for this NPRM. The economic
analysis provides a cost-benefit analysis, as required by Executive
Order 12866. This regulatory flexibility analysis also examines the
potential economic effects of this rule on small entities, as required
by the Regulatory Flexibility Act. The economic analysis is summarized
below. Copies of the full analysis are available at the Supporting
Materials tab of the docket, or at www.select agents.gov.
Summary of the Regulatory Impact Analysis
HHS/CDC has proposed modifications to the list of select agents and
toxins as well as revisions to several of the select agent and toxin
regulations. These proposed revisions to the select agent and toxin
regulations will increase their usability as well as provide for
enhanced program oversight. Specifically, HHS/CDC is proposing to add
definitions for several terms (Discovery, Theft, Loss, Release,
Validated Removal Procedure, Verification viability testing protocol);
codify policies regarding the role of responsible officials and
alternate responsible officials, conclusion of patient care, and annual
internal inspections; and revise or clarify provisions related to
validated inactivation procedures and viable select agent removal
methods, recordkeeping, non-possession of select agents and toxins,
eFSAP, registration, Tier 1 enhancements, and exclusion of naturally
infected animals. HHS/CDC is also proposing to add requirements for
reporting discoveries of select agents and toxins, provisions regarding
effluent decontamination system, biosafety provisions for facility
verification requirements for registered biosafety level 3 and animal
biosafety level 3 laboratories, new requirement related to restricted
experiments, as well as to correct editorial errors. These proposed
changes would economically benefit producers, research and reference
laboratories, and State and Federal oversight agencies, while also
maintaining adequate program oversight of select agents and toxins.
Currently, there are 236 entities registered with APHIS and CDC. Of
these entities, there are 13 Private entities, 30 Federal entities, 42
Commercial entities, 84 Academic entities, and 67 State entities
registered with APHIS and CDC. Less than 4 percent of all firms
operating within these North American Industry Classification (NAICS)
categories are considered to be small entities. The NPRM will not have
a significant economic impact on a substantial number of small
entities.
The benefits of strengthened safeguards against the unintentional
or deliberate release of a select agent or toxin greatly exceed
compliance costs of the rules. As an example of losses that can occur,
the October 2001 anthrax attacks caused 5 fatalities and 17 illnesses,
disrupted business and government activities (including $2 billion in
lost revenues for the Postal Service), and required more than $23
million to decontaminate one Senate office building and $3 billion to
decontaminate postal facilities and procure mail-sanitizing equipment.
Deliberate introduction greatly increases the probability of a select
agent becoming established and causing wide-ranging and devastating
impacts to the economy, other disruptions to society, and diminished
confidence in public and private institutions.
The proposed amendments to the regulations will enhance the
protection of human, animal, and plant health and safety. The proposal
is to reduce likelihood of the accidental or intentional release of a
select agent or toxin. Benefits of the rules will derive from the
greater probability that a release will be prevented from occurring.
B. The Regulatory Flexibility Act (RFA), as Amended by the Small
Business Regulatory Enforcement Fairness Act (SBREFA)
HHS/CDC has examined the impacts of the proposed rule under the
Regulatory Flexibility Act (5 U.S.C. 601-612). Unless HHS/CDC certifies
that the proposed rule is not expected to have a significant economic
impact on a substantial number of small entities, the Regulatory
Flexibility Act (RFA), as amended by the Small Business Regulatory
Enforcement Fairness Act (SBREFA), requires agencies to analyze
regulatory options that would minimize any significant economic impact
of a rule on small entities. HHS/CDC certifies that this proposed rule
will not have a significant economic impact on a substantial number of
small entities within the meaning of the RFA.
This regulatory action is not a major rule as defined by Sec. 804
of the Small Business Regulatory Enforcement Fairness Act of 1996. This
proposed rule will not result in an annual effect on the economy of
$100,000,000 or more; a major increase in cost or prices; or
significant adverse effects on competition, employment, investment,
productivity, innovation, or on the ability of United States-based
companies to compete with foreign-based companies in domestic and
export markets.
C. Paperwork Reduction Act of 1995
In accordance with section 3507(d) of the Paperwork Reduction Act
of 1995 (44 U.S.C. 3501 et seq.), HHS/CDC has determined that the
Paperwork Reduction Act does apply to information collection and
recordkeeping requirements included in this rule. HHS/CDC notes that
the information collection and recordkeeping requirements are already
approved by the Office of Management and Budget (OMB) under OMB Control
Number 0920-0576, expiration 1/31/2024. HHS/CDC will be seeking renewal
of the information collection prior to the publication of the final
rule. HHS/CDC will also pursue OMB approval for the proposed Form 6
through a separate process, through a standard clearance with OMB,
rather than in this rulemaking.
The total estimated annualized burden for all data collection was
calculated using the 2021 Annual Report of the Federal Select Agent
Program available at https://www.selectagents.gov/resources/publications/annualreport/2021.htm or FSAP IT system and is estimated
as 3,655.5 hours and includes additional 30 minutes added to the
average burden per response (in hours) for the training proposal in
accordance with the new mandate in the Consolidated Appropriations Act,
2023, Public Law 117-328 (division H, title II, section 2311),
``Improving Control and Oversight of Select Biological Agents and
Toxins'' (Section 351A of the Public Health Service Act (42 U.S.C.
262a)) amendment of subsection (b)(1). Information will be collected
through FSAP IT system, fax, email and hard copy mail from respondents.
[[Page 5835]]
Estimated Annualized Burden Hours
----------------------------------------------------------------------------------------------------------------
Number of Average burden Total
Section Form name Number of responses per per response burden
respondents respondent (in hours) hours
----------------------------------------------------------------------------------------------------------------
Sections 3 & 4................. Request for 1 1 1 1
Exclusions.
Sections 5 & 6................. Form 4--Report of 917 1 1 917
Identification of a
Select Agent or
Toxin.
Sections 5 & 6................. Form 5--Request of 1 1 1 1
Exemption.
Section 7...................... Form 1--Application 5 1 5 25
for Registration.
Section 7...................... Form 1 Sec 6A-- 144 5 1 720
Amendment to a
Certificate of
Registration.
Section 9...................... Documentation of self- 233 1 1 233
inspection.
Section 10..................... Request for Expedited 1 1 30/60 1
Review.
Section 11..................... Security Plan........ 233 1 1 233
Section 12..................... Biosafety Plan....... 233 1 1 233
Section 13..................... Request Regarding a 3 1 2 6
Restricted
Experiment.
Section 14..................... Incident Response 233 1 1 233
Plan.
Section 15..................... Training............. 233 1.5 1.5 339.5
Section 16..................... Form 2--Request to 229 1 1.5 380
Transfer Select
Agents and Toxins.
Section 17..................... Records.............. 233 1 30/60 117
Section 19..................... Form 3--Notification 185 1 1 185
of Theft, Loss, or
Release.
Section 20..................... Administrative Review 22 1 1 22
--------------------------------------------------------------------------------
Total...................... ..................... ........... .............. ............... 3,655.5
----------------------------------------------------------------------------------------------------------------
D. E.O. 12988: Civil Justice Reform
This rule has been reviewed under E.O. 12988, Civil Justice Reform.
Once the final rule is in effect, HHS/CDC notes that: (1) All State and
local laws and regulations that are inconsistent with this rule will be
preempted; (2) No retroactive effect will be given to this rule; and
(3) Administrative proceedings will not be required before parties may
file suit in court challenging this rule.
E. E.O. 13132: Federalism
HHS/CDC has reviewed this proposed rule in accordance with
Executive Order 13132 regarding Federalism and has determined that it
does not have ``federalism implications.'' The rule does not ``have
substantial direct effects on the States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government.''
In accordance with section 361(e) of the PHSA [42 U.S.C. 264(e)],
nothing in this rule would supersede any provisions of State or local
law except to the extent that such a provision conflicts with this
rule.
F. Plain Language Act of 2010
Under the Plain Language Act of 2010 (Pub. L. 111-274, October 13,
2010), executive Departments and Agencies are required to use plain
language in documents that explain to the public how to comply with a
requirement the Federal Government administers or enforces. HHS/CDC has
attempted to use plain language in promulgating this rule consistent
with the Federal Plain Writing Act guidelines.
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List of Subjects
Biologics, Packaging and containers, Penalties, Reporting and
recordkeeping requirements, Transportation.
For the reasons discussed in the preamble, HHS proposes to amend 42
CFR part 73 as follows:
PART 73--SELECT AGENTS AND TOXINS
0
1. The authority citation for part 73 is revised to read as follows:
Authority: 42 U.S.C. 262a; sections 201-204, 221 and 231 of
Title II of Pub. L. 107-188, 116 Stat. 637 (42 U.S.C. 262a).
Sec. 73.0 [Removed]
0
2. Remove Sec. 73.0.
0
3. Section 73.1 is amended by:
0
a. Adding in alphabetical order definitions for ``Discovery'',
``Loss'', ``Release'', and ``Theft'';
0
b. Revising the definition of ``Validated inactivation procedure'';
0
c. Adding in alphabetical order definitions for ``Validated removal
procedure'' and ``Verification viability testing protocol''; and
0
d. Revising the definition of ``Viability testing protocol''.
The additions and revision read as follows:
Sec. 73.1 Definitions.
* * * * *
Discovery means the finding of a select agent or toxin by an
individual or entity that is not aware of the select agent or toxin's
existence. Examples include, but are not limited to, the following:
(1) A registered individual or entity finds a select agent or toxin
not accounted for in their inventory; or
(2) A non-registered individual or entity finds a select agent or
toxin.
* * * * *
Loss means the inability to account for a select agent or toxin
known to be in the individual or entity's possession.
* * * * *
Release means any of the following:
(1) An incident resulting in occupational exposure to a select
agent or toxin,
(2) An incident resulting in animal/plant exposure to a select
agent or toxin,
(3) The failure of equipment used to contain a select agent or
toxin such that it is reasonably anticipated that a select agent or
toxin was released,
(4) The failure of or breach in personal protective equipment in
the presence of a select agent or toxin, or
(5) The failure of biosafety procedures such that it is reasonably
anticipated
[[Page 5837]]
that a select agent or toxin was outside of containment.
* * * * *
Theft means the unauthorized taking and removing of a select agent
or toxin from the possession of an entity or individual.
* * * * *
Validated inactivation procedure means a procedure, whose efficacy
has been confirmed by data generated from an in-house viability testing
protocol, to render a select agent non-viable but allows the select
agent to retain characteristics of interest for future use; or to
render any nucleic acids that can produce infectious forms of any
select agent virus non-infectious for future use.
* * * * *
Validated removal procedure means a procedure, whose efficacy has
been confirmed by data generated in-house from a viability testing
protocol, to confirm removal of all viable select agent, or nucleic
acids of any select agent virus capable of producing infectious virus.
* * * * *
Verification viability testing protocol means a protocol, used on
samples that have been subjected to a validated inactivation or removal
procedure, to confirm the material is free of all viable select agent,
or nucleic acids of any select agent virus capable of producing
infectious virus.
* * * * *
Viability testing protocol means a protocol used to confirm the
efficacy of the inactivation or removal procedure by demonstrating the
material is free of all viable select agent, or nucleic acids of any
select agent virus capable of producing infectious virus.
* * * * *
0
5. Section 73.2 is revised to read as follows:
Sec. 73.2 Purpose and scope.
(a) This part implements the provisions of the Public Health
Security and Bioterrorism Preparedness and Response Act of 2002 and the
Public Health Service Act, 42 U.S.C. 262a, as amended, setting forth
the requirements for possession, use, and transfer of select agents and
toxins. The biological agents and toxins listed in this part have the
potential to pose a severe threat to public health and safety, to
animal health, or to animal products. Overlap select agents and toxins
are subject to regulation by both CDC and APHIS.
(b) Any individual or entity in possession of a select agent or
toxin, for which an exclusion or exemption listed in this part does not
apply, and that is not included on a certificate of registration issued
by the HHS Secretary or Administrator for that individual or entity,
must immediately report such possession to either the HHS Secretary or
Administrator by the submission of an APHIS/CDC Form 6.
0
6. Section 73.3 is amended by:
0
a. Revising paragraphs (b), (d)(1), and (d)(4) through (6);
0
b. Redesignating paragraphs (d)(7) through (11) as paragraphs as (d)(8)
through (12), respectively.
0
c. Adding new paragraph (d)(7);
0
d. In newly redesignated paragraph (d)(8) introductory text, removing
the text ``100 mg of Conotoxins'' and adding in its place the text
``200 mg of Conotoxins'';
0
e. In newly redesignated paragraph (d)(12) by removing the text ``of
the conclusion of patient care'' and adding in its place ``from when
the individual has been released from the medical facility where
treatment was being provided'';
0
f. In paragraph (e)(1), removing the text ``National Select Agent
Registry website'' and adding in its place ``Federal Select Agent
Program website'';
0
g. In paragraph (f)(3)(i), removing the text ``Bacillus cereus Biovar
anthracis, Botulinum neurotoxins, Botulinum neurotoxin producing
species of Clostridium, Ebola viruses, Francisella tularensis, Marburg
virus, Variola major virus (Smallpox virus), Variola minor (Alastrim),
or Yersinia pestis'' and adding in its place ``Tier 1 agents and
toxins'' and removing the text ``telephone, facsimile, or email'' and
adding in its place the text ``eFSAP information system, telephone, or
email'';
0
h. In paragraph (f)(3)(iii), adding the text ``not submitted through
eFSAP information system'' between the words ``APHIS/CDC Form 4'' and
``must''; and
0
k. In paragraph (f)(4), adding the text ``not submitted through eFSAP
information system'' between the words ``form'' and ``must''.
The revisions and additions read as follows:
Sec. 73.3 HHS select agents and toxins.
* * * * *
(b) HHS select agents and toxins:
Abrin
Bacillus cereus Biovar anthracis *
Botulinum neurotoxins *
Botulinum neurotoxin producing species of Clostridium
Conotoxins (Short, paralytic alpha conotoxins containing the following
amino acid sequence
X1CCX2PACGX3X4X5X
6CX7) \1\
Coxiella burnetii
Crimean-Congo hemorrhagic fever virus \2\
Diacetoxyscirpenol
Eastern equine encephalitis virus \2\
Ebolavirus * \2\
Francisella tularensis *
Lassa fever virus \2\
Lujo virus \2\
Marburg virus * \2\
Mpox virus (clade I) \2\
Reconstructed replication competent forms of the 1918 pandemic
influenza A virus containing any portion of the coding regions of all
eight gene segments (Reconstructed 1918 influenza A virus) \2\
Ricin
Rickettsia prowazekii
Severe acute respiratory syndrome coronavirus (SARS-CoV) \2\
Saxitoxin
South American hemorrhagic fever viruses \2\:
Chapare
Guanarito
Junin
Machupo
Sabia
Staphylococcal enterotoxins (subtypes A,B,C,D,E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus \4\
Far Eastern subtype
Siberian subtype
Kyasanur Forest disease virus \2\
Omsk haemorrhagic fever virus \2\
Variola major virus (Smallpox virus) * \2\
Variola minor virus (Alastrim) * \2\
Yersinia pestis *
\1\ C = Cysteine residues are all present as disulfides, with
the 1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming
specific disulfide bridges; The consensus sequence includes known
toxins a-MI and a-GI (shown above) as well as a-GIA, Ac1.1a, a-CnIA,
a-CnIB; X1 = any amino acid(s) or Des-X; X2 = Asparagine or
Histidine; P = Proline; A = Alanine; G = Glycine; X3 = Arginine or
Lysine; X4 = Asparagine, Histidine, Lysine, Arginine, Tyrosine,
Phenylalanine or Tryptophan; X5 = Tyrosine, Phenylalanine, or
Tryptophan; X6 = Serine, Threonine, Glutamate, Aspartate, Glutamine,
or Asparagine; X7 = Any amino acid(s) or Des X and; ``Des X'' = ``an
amino acid does not have to be present at this position.'' For
example, if a peptide sequence were XCCHPA then the related peptide
CCHPA would be designated as Des-X.
\2\ Please refer to https://www.selectagents.gov for current
information on historical or proposed nomenclature for the HHS
select agents on the list.
* * * * *
(d) * * *
(1) * * * Except for:
(i) Any animal which is naturally infected with a select agent from
its natural environment to an artificially
[[Page 5838]]
established environment for the purpose of the intentional exposure or
introduction of a select agent to a na[iuml]ve or experimental animal;
or
(ii) Any animal which is naturally infected with a select agent for
the purpose of the intentional exposure or introduction of a select
agent to the na[iuml]ve or experimental animal is placed with a
na[iuml]ve animal in their natural environment.
* * * * *
(4) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus that has been subjected to a
validated inactivation procedure, provided that:
(i) In-house validation of the inactivation procedure is completed
prior to use;
(ii) A certificate of inactivation has been generated in accordance
with Sec. 73.17(a)(8);
(iii) For use of a select agent surrogate to validate an
inactivation procedure:
(A) Select agent surrogates must be known to possess equivalent
properties with respect to inactivation;
(B) If there are known variations in the resistance of a select
agent to an inactivation procedure, including strain to strain, then an
inactivation procedure must also be validated using the most resistant
select agent surrogate.
(iv) For use of a whole tissue or homogenized tissue surrogate to
validate a chemical inactivation procedure for other tissues, including
those in other animal models:
(A) All standardized conditions must be held constant, such as the
select agent used, tissue volume, and ratio of tissue to volume of
inactivating chemical;
(B) A safety margin must be incorporated into the final chemical
inactivation procedure to ensure the effective inactivation of the
select agent;
(C) The tissue surrogate must meet the following criteria:
(1) The tissue is expected to have the highest concentration of the
specific select agent to be inactivated; or
(2) The concentration of the select agent in the tissue must be
determined and this select agent concentration must not be exceeded
when applying the validated inactivation procedure on subsequent tissue
samples.
(5) Any select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus contained in a formalin-
fixed paraffin-embedded (FFPE) tissue if the FFPE process used is a
recognized procedure for that particular select agent or regulated
nucleic acids.
(6) Material containing a select agent that is subjected to a
validated viable select agent removal procedure that has rendered the
material free of all viable select agent provided that:
(i) In-house validation of the viable select agent removal
procedure is completed prior to use;
(ii) A certificate of viable select agent removal has been
generated in accordance with Sec. 73.17(a)(8);
(iii) For use of a surrogate to validate a viable select agent
removal procedure, only surrogates known to possess equivalent
properties with respect to removal are used.
(A) Select agent surrogates must be known to possess equivalent
properties with respect to inactivation.
(B) If there are known variations in the resistance of a select
agent to an inactivation procedure, including strain to strain, then an
inactivation procedure must also be validated using the most resistant
select agent surrogate.
(iv) A portion of each subsequent sample has been subjected to a
verification viability testing protocol to ensure that the validated
viable select agent removal procedure has rendered the material free of
all viable select agent.
(7) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus not subjected to a validated
inactivation procedure or material containing a select agent not
subjected to a validated viable select agent removal procedure that
removes all viable select agent cells, spores, or virus particles if
the material is determined by the HHS Secretary to be effectively
inactivated or effectively removed. To apply for a determination, an
individual or entity must submit a written request and supporting
scientific information to APHIS or CDC. A written decision granting or
denying the request will be issued.
* * * * *
0
7. Section 73.4 is amended by:
0
a. Revising paragraphs (b), (d)(1), and (d)(4) through (6);
0
b. Redesignating paragraphs (d)(7) through (9) as paragraphs (d)(8)
through (d)(10), respectively.
0
c. Adding new paragraph (d)(7);
0
d. In newly redesignated paragraph (d)(9), removing the text ``of the
conclusion of patient care'' and adding in its place ``from when the
individual has been released from the medical facility where treatment
was being provided'';
0
e. Revising newly redesignated paragraph (d)(10);
0
f. In paragraph (e)(1), removing the text ``National Select Agent
Registry website'' and adding in its place ``Federal Select Agent
Program website'';
0
g. In paragraph (f)(3)(i), removing the text ``Bacillus anthracis,
Burkholderia mallei and Burkholderia pseudomallei'' and adding in its
place ``Tier 1 agents'' and removing the text ``telephone, facsimile,
or email'' and adding in its place the text ``eFSAP information system,
telephone, or email'';
0
h. In paragraph (f)(3)(iii), adding the text ``not submitted through
eFSAP Information System'' between the text ``APHIS/CDC Form 4'' and
``must'';
0
i. In paragraph (f)(4), adding the text ``not submitted through eFSAP
information system'' between the words ``form'' and ``must''.
The revisions and addition read as follows:
Sec. 73.4 Overlap select agents and toxins.
* * * * *
(b) Overlap select agents and toxins:
Bacillus anthracis *
Bacillus anthracis Pasteur strain
Burkholderia mallei *
Burkholderia pseudomallei *
Hendra virus
Nipah virus *
Rift Valley fever virus
Venezuelan equine encephalitis virus
* * * * *
(d) * * *
(1) Except for:
(i) Any animal which is naturally infected with a select agent from
its natural environment to an artificially established environment for
the purpose of the intentional exposure or introduction of a select
agent to a na[iuml]ve or experimental animal; or
(ii) Any animal which is naturally infected with a select agent for
the purpose of the intentional exposure or introduction of a select
agent to the na[iuml]ve or experimental animal is placed with a
na[iuml]ve animal in their natural environment.
* * * * *
(4) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus that has been subjected to a
validated inactivation procedure, provided that:
(i) In-house validation of the inactivation procedure is completed
prior to use;
(ii) A certificate of inactivation has been generated in accordance
with Sec. 73.17(a)(8);
(iii) For use of a select agent surrogate to validate an
inactivation procedure:
(A) Select agent surrogates must be known to possess equivalent
properties with respect to inactivation;
(B) If there are known variations in the resistance of a select
agent to an inactivation procedure, including strain to strain, then an
inactivation procedure
[[Page 5839]]
must also be validated using the most resistant select agent surrogate;
(iv) For use of a whole tissue or homogenized tissue surrogate to
validate a chemical inactivation procedure for other tissues, including
those in other animal models:
(A) All standardized conditions must be held constant, such as the
select agent used, tissue volume, and ratio of tissue to volume of
inactivating chemical;
(B) A safety margin must be incorporated into the final chemical
inactivation procedure to ensure the effective inactivation of the
select agent;
(C) The tissue surrogate must meet the following criteria:
(1) The tissue is expected to have the highest concentration of the
specific select agent to be inactivated; or
(2) The concentration of the select agent in the tissue must be
determined and this select agent concentration must not be exceeded
when applying the validated inactivation procedure on subsequent tissue
samples.
(5) Any select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus contained in a FFPE tissue
if the FFPE process used is a recognized procedure for that particular
select agent or regulated nucleic acids.
(6) Material containing a select agent that is subjected to a
validated viable select agent removal procedure to ensure that the
validated viable select agent removal procedure has rendered the
material free of all viable select agent except for:
(i) In-house validation of the viable select agent removal
procedure is completed prior to use;
(ii) A certificate of viable select agent removal has been
generated in accordance with Sec. 73.17(a)(8);
(iii) For use of a surrogate to validate a viable select agent
removal procedure, only surrogates known to possess equivalent
properties with respect to removal are used; and
(iv) A portion of each subsequent sample has been subjected to a
verification viability testing protocol to ensure that the validated
viable select agent removal procedure has rendered the material free of
all viable select agent.
(7) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus not subjected to a validated
inactivation procedure or material containing a select agent not
subjected to a validated viable select agent removal procedure that
removes all viable select agent cells, spores, or virus particles if
the material is determined by the HHS Secretary to be effectively
inactivated or effectively removed. To apply for a determination an
individual or entity must submit a written request and supporting
scientific information to APHIS or CDC. A written decision granting or
denying the request will be issued.
* * * * *
0
8. Section 73.5 is amended as follows:
0
a. By revising paragraph (a)(1);
0
b. In paragraph (a)(3) by removing the text ``delivery of patient
(i.e., human) care by health care professionals has concluded'' and
adding in its place ``the individual has been released from the medical
facility where treatment was being provided''.
0
c. By revising paragraph (a)(4)(i);
0
d. In paragraph (a)(4)(iv) by adding the text ``not submitted through
eFSAP Information System'' between the text ``APHIS/CDC Form 4'' and
``must'';
0
e. In paragraph (b) introductory text by removing the article ``a'' and
adding in its place the article ``an'' before ``HHS'';
0
f. By revising paragraph (b)(1); and
0
g. In the last sentence of paragraph (b)(3) by adding the text ``not
submitted through eFSAP Information System'' between the words ``form''
and ``must''.
The revisions read as follows:
Sec. 73.5 Exemptions for HHS select agents and toxins.
(a) * * *
(1) Unless directed otherwise by the HHS Secretary, within seven
calendar days after identification of the select agent or toxin (except
for Botulinum neurotoxin), or within 30 calendar days after
identification of Botulinum neurotoxin, the select agent or toxin is
transferred in accordance with Sec. 73.16 or destroyed on-site by a
recognized sterilization process or inactivated for future use in
accordance with section 73.3 (d)(4).
* * * * *
(4) The identification of the agent or toxin is reported to CDC or
APHIS, the specimen provider, and to other appropriate authorities when
required by Federal, State, or local law through the eFSAP information
system, telephone, or email. This report must be followed by submission
of APHIS/CDC Form 4 to APHIS or CDC within seven calendar days after
identification.
(i) The identification of HHS Tier 1 select agents or toxin must be
immediately reported through the eFSAP information system, telephone,
or email. This report must be followed by submission of APHIS/CDC Form
4 within seven calendar days after identification.
* * * * *
(b) * * *
(1) Unless directed otherwise by the HHS Secretary, within 90
calendar days of receipt, the select agent or toxin is transferred in
accordance with Sec. 73.16 or destroyed on-site by a recognized
sterilization process or inactivated for future use in accordance with
Sec. 73.3(d)(4).
* * * * *
0
9. Section 73.6 is amended as follows:
0
a. By revising paragraphs (a) introductory text and (a)(1);
0
b. In paragraph (a)(3) by removing the text ``delivery of patient care
by health care professionals has concluded'' and adding in its place
``the individual has been released from the medical facility where
treatment was being provided'';
0
c. By revising paragraph (a)(4)(i);
0
d. In paragraph (a)(4)(iv) by adding the text ``not submitted through
eFSAP information system'' between ``APHIS/CDC Form 4'' and ``must'';
0
e. By revising paragraph (b)(1); and
0
f. In the last sentence of paragraph (b)(3) by adding the text ``not
submitted through eFSAP information system'' between the words ``form''
and ``must''.
The revisions read as follows:
Sec. 73.6 Exemptions for overlap select agents and toxins.
(a) Clinical or diagnostic laboratories and other entities that
possess, use, or transfer an overlap select agent or toxin that is
contained in a specimen presented for diagnosis or verification will be
exempt from the requirements of this part for such agent or toxin
contained in the specimen, provided that:
(1) Unless directed otherwise by the HHS Secretary or
Administrator, within seven calendar days after identification, the
select agent or toxin is transferred in accordance with Sec. 73.16 or
9 CFR 121.16 or destroyed on-site by a recognized sterilization
process, or inactivated for future use in accordance with Sec.
73.4(d)(4),
* * * * *
(4) The identification of the agent or toxin is reported to CDC or
APHIS, the specimen provider, and to other appropriate authorities when
required by Federal, State, or local law through the eFSAP information
system, telephone, or email. This report must be followed by submission
of APHIS/CDC Form 4 to APHIS or CDC within seven calendar days after
identification.
(i) The identification of overlap Tier 1 select agents or toxin
must be immediately reported through the eFSAP information system,
telephone, or email. This report must be followed by submission of
APHIS/CDC Form 4
[[Page 5840]]
within seven calendar days after identification.
* * * * *
(b) * * *
(1) Unless directed otherwise by the HHS Secretary or
Administrator, within 90 calendar days of receipt, the select agent or
toxin is transferred in accordance with Sec. 73.16 or 9 CFR part
121.16 or destroyed on-site by a recognized sterilization process or
inactivated for future use in accordance with Sec. 73.4 (d)(4),
* * * * *
0
10. Section 73.7 is amended as follows:
0
a. In paragraph (f) by removing ``the relevant page(s) of'' and adding
in its place ``information related to'';
0
b. By revising paragraph (g);
0
c. In paragraph (i) by removing the word ``may'' and adding in its
place the word ``must'' and by removing the word ``circumstances'' and
adding in its place the phrase ``the possession and use of the select
agents and toxins''; and
0
d. In paragraph (i)(1) by removing ``the relevant page(s) of'' and
adding in its place ``information related to''.
The revision reads as follows:
Sec. 73.7 Registration and related security risk assessments.
* * * * *
(g) The issuance of a certificate of registration may be contingent
upon inspection and submission of additional information to include any
or all of the following: the security plan, biosafety plan, incident
response plan, or any other information related to the requirements of
this part.
* * * * *
0
11. Section 73.9 is amended as follows:
0
a. By redesignating paragraphs (a)(5) through (9) as paragraphs as
(a)(6) through (10);
0
b. By adding new paragraph (a)(5);
0
c. By revising newly redesignated paragraphs (a)(7), (9), and (10);
0
d. In paragraph (b) by adding a new second sentence;
0
e. By revising paragraph (c)(1); and
0
f. In the last sentences of paragraphs (c)(2) and (d) by adding the
phrase ``not submitted through eFSAP information system'' between the
words ``form'' and ``must''.
The addition and revision read as follows:
Sec. 73.9 Responsible Official.
* * * * *
(a) * * *
(5) Not be approved as Responsible Official or alternate
Responsible Official at another registered entity,
* * * * *
(7) Ensure that annual inspections are conducted for each
registered space to determine compliance with the requirements in
accordance with the regulations of this part. The results of each
inspection must be documented, and any deficiencies identified during
an inspection must be corrected and the corrections documented. The
annual inspection must address whether:
(i) The entity's biosafety/biocontainment plan is being effectively
implemented, as outlined in Sec. 73.12.
(ii) The entity's security plan is being effectively implemented,
as outlined in Sec. 73.11.
(iii) The entity's incident response plan is implemented to ensure
whether the entity is able to respond, as outlined in Sec. 73.14.
(iv) Each individual with access approval from the HHS Secretary or
Administrator has received the appropriate training as outlined in
Sec. 73.15.
* * * * *
(9) Investigate to determine the reason for any failure of a
validated inactivation or validated viable select agent removal
procedure to render material free from viable select agent. If the
Responsible Official is unable to determine the cause of the failure
from a validated inactivation or validated viable select agent removal
procedure or receives a report of any inactivation failure after the
movement of material to another location, the Responsible Official must
report immediately through the eFSAP information system, telephone or
email the inactivation or viable select agent removal procedure failure
to CDC or APHIS.
(10) Review each of the entity's validated select agent
inactivation procedure or validated viable select agent removal
procedure and ensure they are revised as necessary. The review must be
conducted annually or after any change in Principal Investigator,
change in the validated inactivation or validated viable select agent
removal procedure, or failure of the validated inactivation or
validated viable select agent removal procedure. The review must be
documented, and training must be conducted if there are any changes to
the validated select agent inactivation or validated viable select
agent removal procedure, or viability testing protocol.
(b) * * * An alternate Responsible Official can serve at multiple
registered entities. * * *
(c) * * *
(1) The identification of any Tier 1 agents or toxins must be
immediately reported through the eFSAP information system, telephone,
or email. The final disposition of the agent or toxin must be reported
by submission of APHIS/CDC Form 4 within seven calendar days after
identification (except for Botulinum neurotoxin and/or Staphylococcal
enterotoxin (Subtypes A-E)), which is within 30 calendar days after
identification). A copy of the completed form not submitted through
eFSAP information system must be maintained for three years.
* * * * *
Sec. 73.10 [Amended]
0
12. Section 73.10 is amended in paragraph (c) by removing the words
``to select agents or toxins'' and adding in their place ``access
approval from the HHS Secretary or Administrator''.
0
13. Section 73.11 is amended as follows:
0
a. By redesignating paragraphs (c)(9) and (10) as paragraphs (c)(10)
and (11);
0
b. By adding a new paragraph (c)(9);
0
c. In paragraph (d)(4) by removing the text ``the area where select
agents or toxins are used or stored'' and adding in its place
``registered space'';
0
d. In paragraph (f) introductory text by removing the word
``possessing'' and adding in its place ``registered for'';
0
e. In paragraph (f)(1) by removing the words ``will have'' and adding
in their place ``are registered for'';
0
f. By revising paragraph (f)(4)(iii); and
0
g. By removing paragraph (g) and redesignating paragraph (h) as
paragraph (g).
The addition and revision read as follows:
Sec. 73.11 Security.
* * * * *
(c) * * *
(9) Describe procedures to prevent the theft, loss, or unauthorized
access to a select agent or toxin from an effluent decontamination
system originating from a registered laboratory.
* * * * *
(f) * * *
(4) * * *
(iii) Procedures for screening visitors, their property, and, where
appropriate, vehicles at entry and exit points to registered space
based on the entity's site-specific risk assessment;
* * * * *
0
14. Section 73.12 is amended as follows:
0
a. In paragraphs (c)(1) and (2) by removing the words ``National Select
Agent Registry website'' and adding in their place ``Federal Select
Agent Program website'';
0
b. By revising paragraph (d); and
0
c. By adding paragraphs (f), (g), and (h).
[[Page 5841]]
The revision and additions read as follows:
Sec. 73.12 Biosafety.
* * * * *
(d) The biosafety plan must include an occupational health plan for
individuals listed on the individual or entity's registration for
access to Tier 1 select agents and toxins, and those individuals must
be enrolled in the occupational health plan.
* * * * *
(f) When an effluent decontamination system is used, the plan must
provide for verification that the liquid waste generated from
registered space is sufficiently treated to prevent the release of a
select agent or toxin prior to discharge of the waste from the
facility.
(1) For a new effluent decontamination system, verification is
required before initial use.
(2) For an effluent decontamination system in place, verification
is required at least once every 12 months and following any major
change to the effluent decontamination system.
(3) The verification must be documented.
(g) When an effluent decontamination system is used, the plan must
provide that monthly routine maintenance is conducted of the effluent
decontamination system, including at a minimum verification that:
(1) Alarms are functioning according to established specifications;
(2) Piping, pumps, valves, and tanks are not leaking; and
(3) Methods used to monitor and record performance measurements and
are functioning according to established specifications.
(h) An individual or entity must document every 12 months the
following facility verification requirements for registered biosafety
level 3 and animal biosafety level 3 laboratories.
(1) Accuracy of devices that monitor directional air-flow;
(2) Confirmation that decontamination systems (e.g., autoclave,
room decontamination systems, digesters, liquid effluent
decontamination systems) are operating to ensure the containment of the
select agent and toxin;
(3) Confirmation that systems are in place to monitor, maintain and
validate performance of mechanical systems to ensure that airflows and
differential pressures are appropriate to maintain containment during
normal/operational conditions;
(4) Verification that the facility mechanical, electrical, and
drain waste and ventilation systems responsible for containment are
inspected, maintained, and function as designed manufacturer
specifications;
(5) Verification that the facility systems perform as intended in
response to failure conditions as defined and tested during
commissioning to prevent the release of select agent or toxin and
verify secondary containment:
(i) Evaluate using work objectives, use of space, and facility
infrastructure systems against the verified original design and
standards (e.g., Biosafety in Microbiological and Biomedical
Laboratories, NIH Design Requirements Manual).
(ii) Implement controls and alarms to identify and alert personnel
when systems fail, malfunction, or are unable to maintain containment
during such an event.
(6) Certification of laboratory ventilation system HEPA filters, if
present;
(7) Confirmation that room integrity has been evaluated and repairs
are addressed (e.g., sealed penetrations);
(8) Primary containment equipment is certified based on
manufacturer's specifications (or recommendations) (e.g., biological
safety cabinets, flexible film isolators, animal caging);
(9) Seals on centrifuges not used in primary containment have been
checked and replaced if needed; and
(10) Showers, eye wash stations, and hands-free sinks are operating
properly.
Sec. 73.13 [Amended]
0
15. Section 73.13 is amended in paragraph (a) introductory text by
adding ``or transfer'' after ``possess''.
0
16. Section 73.14 is amended as follows:
0
a. In paragraph (b) by adding the words ``the failure of an effluent
decontamination system resulting in a release of a select agent or
toxin;'' after ``a select agent or toxin;'';
0
b. By revising paragraph (c); and
0
c. In paragraph (e) introductory text by removing the words ``Entities
with'' and adding in their place ``An individual or entity registered
for''.
The revision reads as follows:
Sec. 73.14 Incident response.
* * * * *
(c) The response procedures must account for hazards associated
with the select agent or toxin and appropriate actions to contain such
select agent or toxin in registered space including any animals
(including arthropods) or plants intentionally or accidentally exposed
to or infected with a select agent, or an effluent decontamination
system originating from registered space.
* * * * *
0
17. Section 73.15 is amended as follows:
0
a. By adding paragraphs (a)(3) and (4);
0
b. In paragraph (b) by removing the words ``Entities with'' and adding
in their place ``An individual or entity registered for''; and
0
c. By revising paragraph (d).
The additions and revision read as follows:
Sec. 73.15 Training.
* * * * *
(a) * * *
(3) Each individual not approved for access to HHS and overlap
select agents and toxins by the HHS Secretary or APHIS Administrator
whose responsibilities routinely place them in close proximity (e.g.,
shared laboratory space) to areas where select agents or toxins are
transferred, possessed, or used. The training must be based on the
particular needs of the individual and risks associated with working
near areas where select agents and toxins are handled or stored. The
training must also instruct each individual on the notification
requirements related to select agents and toxins. Training must be
accomplished prior to the individual's close proximity to areas where
select agents or toxins are handled or stored and refresher training
must be provided annually.
(4) Each individual not approved for access to HHS and overlap
select agents and toxins by the HHS Secretary or APHIS Administrator
who performs administrative or oversight functions of the facility
related to the transfer, possession or use of such agents or toxins on
behalf of the entity (e.g., administrative professionals, facility
managers, etc.). The training must instruct each individual on the
regulatory requirements relevant to their administrative or oversight
functions. The training must also instruct each individual on the
notification requirements related to select agents and toxins. Training
must be accomplished prior to the individual performing these functions
and refresher training must be provided annually.
(d) The Responsible Official must ensure a record of the training
provided for each individual listed in paragraph (a) of this section is
maintained. The record must include the name of the individual who
received the training, the date of the training, a description of the
training provided, and the means used to verify that the individual
understood the training.
* * * * *
[[Page 5842]]
Sec. 73.16 Amended]
0
18. Section 73.16 is amended in paragraph (l) introductory text by
removing the article ``a'' and adding in its place the article ``an''
before ``HHS''.
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19. Section 73.17 is amended as follows:
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a. By revising paragraphs (a)(1), (2), (3), and (8);
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d. By removing the last sentence from paragraph (c); and
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e. By adding paragraph (d).
The revisions and addition read as follows:
Sec. 73.17 Records.
* * * * *
(a) * * *
(1) An accurate, current inventory for each select agent (including
viral genetic elements, recombinant and/or synthetic nucleic acids, and
organisms containing recombinant and/or synthetic nucleic acids) held
in long-term storage (placement in a system designed to ensure
viability for future use, such as in a freezer or lyophilized
materials), including:
(i) The name and characteristics (e.g., strain designation, GenBank
Accession number);
(ii) The quantity acquired from another individual or entity (e.g.,
containers, vials, tubes), date of acquisition, by whom, and the
source;
(iii) Location where it is stored (e.g., building, room number or
name, and freezer identification or other storage container);
(iv) The date the agent was removed and returned, the purpose for
using the agent, the name of the individual who removed and returned
the agent, and when applicable, date of final disposition of the agent
and by whom;
(v) Records created under Sec. 73.16;
(vi) For intra-entity transfers (sender and the recipient are
covered by the same certificate of registration), name of the select
agent, the date of the transfer, the number of items transferred, the
name of the sender, and the name of the recipient; and
(vii) Records created under Sec. 73.19.
(2) An accurate, current accounting of any animals or plants
intentionally or accidentally exposed to or infected with a select
agent (including number and species, location, and appropriate
disposition);
(3) Accurate, current inventory for each toxin held, including:
(i) The name and characteristics;
(ii) The quantity acquired from another individual or entity (e.g.,
containers, vials, tubes, volume including concentration), date of
acquisition, by whom, and the source;
(iii) The initial and current amount (e.g., milligrams,
milliliters, grams);
(iv) Location where the toxin is stored (e.g., building, room
number or name, and freezer identification or other storage container);
(v) When the toxin was accessed, the name of the toxin, the
location where the toxin was accessed, the date the toxin was accessed,
the purpose for accessing the toxin, the name of the individual
accessing the toxin, the date the toxin was returned back to storage,
the name of the individual returning the toxin back to storage, and
date of final disposition of the toxin and by whom;
(vi) Records created under Sec. 73.16;
(vii) For intra-entity transfers (sender and the recipient are
covered by the same certificate of registration), name of the toxin,
the date of the transfer, the number of vials transferred, the date of
transfer, the name of the sender, and the name of the recipient; and
(viii) Records created under Sec. 73.19.
* * * * *
(8) For select agents or material containing select agents or
regulated nucleic acids that can produce infectious forms of any select
agent virus that have been subjected to a validated inactivation
procedure or a validated viable select agent removal procedure:
(i) A written description of the validated inactivation procedure
or validated viable select agent removal procedure used, including
validation data;
(ii) A written description of the viability testing protocol used;
(iii) A written description of the investigation conducted by the
entity's Responsible Official involving a validated inactivation or
validated viable select agent removal failure and the corrective
actions taken;
(iv) The name of each individual performing the validated select
agent inactivation or validated viable select agent removal;
(v) The date(s) the validated inactivation or validated viable
select agent removal was completed;
(vi) The location where the validated inactivation or validated
viable select agent removal was performed; and
(vii) A signed certificate. The certificate must:
(A) Include the date(s) the validated inactivation or validated
viable select agent removal was completed;
(B) Include the validated inactivation procedure or validated
viable select agent removal procedure used;
(C) Include the name of the principal investigator;
(D) Include an attestation statement certifying that the
information on the certificate is true, complete, and accurate, and
that the validated inactivation or validated viable select agent
removal was performed as described in paragraph (a)(8)(i) of this
section;
(E) Be signed by the principal investigator or designee within 7
days after completion of the validated inactivation or validated viable
select agent removal. Such designee must be listed on the entity's
registration and have the knowledge and expertise to provide scientific
and technical direction regarding the validated inactivation procedure
or the validated viable select agent removal procedure to which the
certificate refers;
(F) Be maintained for as long as the material is in the possession
of the registered individual or entity plus an additional 3 years;
(G) A copy of the certificate must accompany all transfers of
inactivated or select agent removed material, including intra-entity
transfers.
* * * * *
(d) All records created in accordance with the regulations of this
part must be maintained for 3 years unless otherwise stated.
Sec. 73.19 [Amended]
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20. Section 73.19 is amended in paragraphs (a)(1) introductory text and
(b)(1) introductory text by adding ``eFSAP information system,'' before
the word ``telephone'' and removing the word ``email'' and adding in
its place ``email''.
Dated: January 22, 2024.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2024-01513 Filed 1-26-24; 8:45 am]
BILLING CODE 4163-18-P