Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review, 15087-15092 [2020-05477]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 85, Number 52 (Tuesday, March 17, 2020)]
[Proposed Rules]
[Pages 15087-15092]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-05477]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 73

[Docket No. CDC-2020-0024]
RIN 0920-AA71


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

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Advance notice of proposed rulemaking and request for comments.

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SUMMARY: In accordance with section 351a of the Public Health Service 
Act, the Centers for Disease Control and Prevention (CDC) in the 
Department of Health and Human Services (HHS; hereafter referred to as 
HHS/CDC) has initiated a review of the HHS list of biological agents 
and toxins that have the potential to pose a severe threat to public 
health and safety (HHS select agents and toxins). This review was 
initiated within two years of the completion of the previous review. In 
reviewing the list, HHS/CDC is considering whether to propose amending 
the HHS list of select agents and toxins.

DATES: Comments should be received on or before May 18, 2020.

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 Select Agents and Toxins, Centers for 
Disease Control and Prevention, 1600 Clifton Road NE, Mailstop H21-7, 
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 https://www.regulations.gov, including any 
personal information provided.
    Docket Access: For access to the docket to read background 
documents or comments received, or to download an electronic version of 
the advance notice of proposed rulemaking, go to https://www.regulations.gov. Comments will be available for public inspection 
Monday through Friday, except for legal holidays, from 9 a.m. until 5 
p.m. at 1600 Clifton Road NE, Atlanta, GA, 30329. Please call ahead to 
1-866-694-4867 and ask for a representative in the Division of Select 
Agents and Toxins (DSAT) to schedule your visit. Please be aware that 
comments and other submissions from members of the public are made 
available for public viewing without changes.

FOR FURTHER INFORMATION CONTACT: Samuel S. Edwin Ph.D., Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE, Mailstop H21-7, Atlanta, Georgia 
30329. Telephone: (404) 718-2000.

SUPPLEMENTARY INFORMATION: The preamble to this advance notice of 
proposed rulemaking is organized as follows:

I. Public Participation
II. Background
III. Modifications to the List of Select Agents and Toxins Being 
Considered
    A. Agents and Toxins Under Consideration
    i. Botulinum Neurotoxin Producing Species of Clostridium
    ii. Coxiella burnetii
    iii. Rickettsia prowazekii
    iv. Bacillus anthracis (Pasteur Strain)
    v. Brucella Abortus, Brucella Melitensis, and Brucella Suis
    vi. Venezuelan Equine Encephalitis Virus (VEEV) 1AB and 1C
    vii. Short, Paralytic Alpha Conotoxins
    viii. Diacetoxyscirpenol
    ix. Staphylococcal Enterotoxins
    x. New World Hantaviruses:
    1. Sin Nombre Virus
    2. Andes Virus
    xi. Old World Hantaviruses:
    1. Hantaan Virus
    2. Dobrava Virus
    B. Toxins Being Considered for Revision to Exclusion Amounts 
(i.e., the Amount Below Which the Toxin Is Not Subject to Regulatory 
Oversight)
    i. Saxitoxin
    ii. Tetrodotoxin
    iii. Botulinum neurotoxin
    C. Designating Nipah Virus as a Tier 1 Select Agent
    IV. 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 advance notice of proposed 
rulemaking.
    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.

II. Background

    Under the Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 (Bioterrorism Response Act) (42 U.S.C. 
262a(a)(1)), 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. In determining whether to include a 
biological agent or toxin on the list, the Bioterrorism Response Act 
(42 U.S.C. 262a(a)(1)(B)) 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.
    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

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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.
    The results of the previous biennial review, discussed in a final 
rule published in the Federal Register on January 19, 2017 (82 FR 
6278), were that HHS/CDC would make no changes to the list of HHS 
select agents and toxins at that time. Given that HHS/CDC is again 
considering whether to remove select agents and toxins as proposed in a 
previous notice of proposed rulemaking (81 FR 2805, January 19, 2016), 
HHS/CDC will consider the 35 public comments received from that notice 
as part of this biennial review. The current list of HHS select agents 
and toxins can be found at 42 CFR 73.3 (HHS select agents and toxins) 
and 42 CFR 73.4 (Overlap select agents and toxins), and is available at 
https://www.selectagents.gov/SelectAgentsandToxinsList.html.
    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 Sec.  73.4 (overlap select agents and 
toxins) have not only the potential to pose a severe threat to human 
health and safety; but have 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 agent or toxin'' 
to mean a biological agent or toxin that is listed pursuant to 42 
U.S.C. 262a and is listed pursuant to 7 U.S.C. 8401. See 7 U.S.C. 8411. 
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 USDA biennial review.

III. Modifications to the List of Select Agents and Toxins Being 
Considered

    The purpose of this advance notice of proposed rulemaking is to 
seek public comment on potential changes to the current list of HHS and 
overlap select agents and toxins. Specifically, we are providing an 
opportunity for interested persons to submit comments, including peer 
reviewed research data, that will better inform us as to whether there 
are: (1) Any biological agents or toxins that should be added to the 
select agents and toxin list because they have the potential to pose a 
severe threat to public health and safety; and (2) biological agents or 
toxins currently on the list that should be removed because they would 
no longer be considered to have the potential to pose a severe threat 
to public health and safety.
    In addition, HHS/CDC is seeking comment on the following specific 
changes to the list of HHS and overlap select agents under 
consideration:

A. Select Agents and Toxins Under Consideration

i. 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). As such, the organism 
itself does not normally cause disease. HHS/CDC is seeking any 
information that will help inform our deliberations regarding if 
Clostridium botulinum should be treated consistently with the 
regulation of other select toxins in which a toxin is regulated but not 
the organism that produces the toxin. For example, Staphylococcus 
aureus is not listed as a select agent, yet Staphylococcal enterotoxins 
A,B,C,D,E subtypes are regulated toxins.
    Should Botulinum neurotoxin producing species of Clostridium be 
removed or retained as an HHS select agent? Please provide a detailed 
explanation for your response.
ii. Coxiella burnetii
    Q fever is a disease caused by the bacteria Coxiella burnetii. Q 
fever is an acute febrile disease that varies in severity and duration. 
Based on the criteria for listing select agents specified under 42 
U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments from the public to 
provide any information not included below to help inform our 
deliberations regarding C. burnetii:
     Q fever has a low mortality rate (<=2%) with antibiotic 
treatment (Rolain et al., 2005). C. burnetii is susceptible to a number 
of readily available antibiotics including tetracycline or doxycycline 
(Rolain et al., 2005).
     Only 0.2-0.5% of the Q fever cases progress past the acute 
infection stage (Cutler, 2007).
     A whole-cell killed vaccine (Q-Vax) is licensed in 
Australia and has been used to vaccinate U.S. researchers who were at 
risk (Seqiris Pty Ltd PV, 2014).
    Should C. burnetii be removed or retained as an HHS select agent? 
Please provide a detailed explanation for your response.
iii. Rickettsia prowazekii
    Rickettsia prowazekii causes epidemic typhus, which is a louse-
borne disease. In 2012, HHS/CDC decided to retain R. prowazekii based 
in part in anticipation of studies being conducted that would help HHS/
CDC to better understand the potential risk of an intentional release 
of this organism. As of 2019, these studies had not been conducted. 
Based on the criteria for listing select agents specified under 42 
U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments from the public to 
provide any information not included below to help inform our 
deliberations regarding R. prowazekii:
     Transmissibility from person-to-person is low because R. 
prowazekii is usually transmitted via blood, although it can be spread 
through inhalation of louse feces (ID50), the concentration 
for human inhalation routes is unknown, but is estimated to be 10\3\-
10\6\ organisms based on non-human primate and other animal studies 
(Eremeeva et al., 2005, Pike, 1976 and Walker, 2003, Reynolds et al., 
2003 and International Cooperation in Animal Biologics, 2004).
     This agent is difficult to grow and purify in quantities 
that would make it a viable biological weapon (Woodman et al., 1977).
     R. prowazekii is susceptible to readily available 
antibiotics and can be treated with a single dose of doxycycline when 
symptoms are present (Raoult et al., 1991).
     When grown in a laboratory, it is difficult to maintain 
the stability of the organism and therefore it would be difficult to 
disseminate efficiently to cause mass exposure or disease that would 
have a significant public health impact (Bovarnick et al., 1950).
    Should R. prowazekii be removed or retained as an HHS select agent? 
Please provide a detailed explanation for your response.
iv. Bacillus anthracis (Pasteur Strain)
    Bacillus anthracis is the bacteria that causes anthrax, an acute 
disease in animals and humans. In order to cause the disease anthrax, 
B. anthracis requires two plasmids, pX01 and pX02, which carry toxin 
and capsule genes (Luna et al., 2006). B. anthracis (Pasteur strain) 
lacks the pX01 plasmid that is needed to cause the disease (Ivins et 
al., 1986). HHS/CDC excluded the B. anthracis (Sterne strain) in 2003 
because the strain lacks the pX02

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plasmid that encodes for the capsule. However, HHS/CDC has retained B. 
anthracis (Pasteur strain) to date because of a concern that someone 
working in a laboratory could combine the Pasteur strain with the 
Sterne strain to produce the wild type phenotype B. anthracis de novo, 
a select agent. Based on the criteria for listing select agents 
specified under 42 U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments 
from the public to provide any information to help inform our 
deliberations regarding if B. anthracis (Pasteur strain) should be 
removed or retained as an HHS select agent? Please provide a detailed 
explanation for your response.
v. Brucella abortus, Brucella melitensis, and Brucella suis
    Based on the criteria for listing select agents specified under 42 
U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments from the public to 
provide any information not included below to help inform our 
deliberations regarding B. abortus, B. melitensis, and B. suis:
     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).
     Disease caused by these bacteria is treatable with 
antibiotics (Spickler, 2018).
     There is no indication that Brucella is transmitted 
between people by casual contact under ordinary condition. 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).
     Brucellosis causes mild clinical symptoms (flu-like 
illness); incubation periods typically range from 1 to 4 weeks, but can 
extend to 6 months (Olsen et al., 2018).
    Should B. abortus, B. melitensis, and B. suis be removed or 
retained as an HHS select agent? Please provide a detailed explanation 
for your response.
vi. Venezuelan Equine Encephalitis Virus (VEEV) 1AB and 1C
    VEEV usually causes mild to severe influenza-like symptoms. Based 
on the criteria for listing select agents specified under 42 U.S.C. 
262a(a)(1)(B), HHS/CDC is seeking comments from the public to provide 
any information not included below to help inform our deliberations 
regarding VEEV 1AB and 1C:
     Case fatality rate is less than 0.7%. Serosurvey data from 
the 1995 Venezuelan 1C outbreak indicated that, of 75,000 estimated 
human cases, one-third reported to a clinic or hospital, and 3,000 (4%) 
were hospitalized for neuroinvasive disease (sequelae), demonstrating 
that two-thirds of the cases [in the 1995 outbreak] were mild or 
asymptomatic (Rivas et al., 1997).
     While it is theoretically possible for VEEV to be spread 
between humans since the virus is found in the pharynx of 6 to 40% of 
acutely ill patients, there is no documented evidence of human-to-human 
transmission (Smith et al., 2009).
     An effective equine vaccine is available and a range of 
humanized monoclonal antibodies are currently available for emergency 
use (Weaver et al., 1996). Restricted animal movement, insecticide 
application, and equine vaccinations are a part of effective control 
measures to contain VEE outbreaks and mitigate the spread of disease 
from equine to humans.
    Should VEEV 1AB and 1C be removed or retained as an HHS select 
agent? Please provide a detailed explanation for your response.
vii. Short, Paralytic Alpha Conotoxins
    Predatory cone snails (genus Conus) produce a rich array of venoms 
(conotoxins) that collectively contain an estimated 100,000 small, 
disulfide-rich peptides neurotoxins (Bulaj, 2008). Short, paralytic 
alpha conotoxins containing the following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7 are a group of neurotoxic peptides isolated 
from the venom of the marine cone snail, genus Conus. Based on the 
criteria for listing select agents specified under 42 U.S.C. 
262a(a)(1)(B), HHS/CDC is seeking comments from the public to provide 
any information not included below to help inform our deliberations 
regarding short, paralytic alpha conotoxins:
     Production of pure preparations (chemical synthesis of 
larger quantities of appropriately folded peptides) is a challenge due 
to the thermodynamic instability of many conotoxins (Purcell et al., 
2012) and most alpha-conotoxins harvested from the venom bulbs of cone 
snails are inactive precursors that are not in the functional form of 
the select toxin. To generate the functional form, soluble peptides of 
the appropriate amino acid sequence must be treated with proteases to 
properly fold and activate the toxin, which requires higher-level 
technical expertise and is a slow process involving several months (Wu 
et al., 2013).
     The optimal route of exposure for toxicity for conotoxins 
is through injection. However, even though there is currently no 
published literature to support conotoxins being administered via the 
inhalation route to achieve a toxic effect, the LD50 (dose 
required to kill half the members of a tested population after a 
specified test duration) is estimated at 20 [mu]g/kg by inhalation 
(Thapa et al., 2014).
    Should conotoxins (short, paralytic alpha conotoxins containing the 
following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7) be removed or retained as a select toxin? 
If retained, should the exclusion amount for conotoxins be increased or 
decreased? Please provide a detailed explanation for your response.
viii. Diacetoxyscirpenol (DAS)
    DAS, a derivative of tetracyclic sesquiterpenes called 
trichothecenes, is produced from strains of Fusarium sambucinum and 
related species that grow on barley, corn, oats, rye, or wheat. In 
2005, HHS/CDC retained DAS because of limited understanding of the risk 
at the time of whether DAS has the potential to pose a severe threat to 
public health. The estimated LD50 of DAS for rodents is 2 to 
16 mg/kg (Knutsen, H.K., et al., 2018).
    Based on the criteria for listing select agents specified under 42 
U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments from the public to 
provide any information to help inform our deliberations regarding DAS. 
Should DAS be removed or retained as a select toxin? If retained, 
should the DAS exclusion amount be increased or decreased? Please 
provide a detailed explanation for your response.
ix. Staphylococcal Enterotoxins
    Staphylococcus aureus produces a number of exotoxins, one of which 
is Staphylococcal enterotoxin B, or SEB. SEB normally exerts its effect 
on the intestines and therefore is referred to as an enterotoxin. SEB 
is one of the pyrogenic toxins (causing fever) that commonly causes 
food poisoning in humans after the toxin is produced in improperly 
handled foodstuffs and subsequently ingested. Based on the criteria for 
listing select agents specified under 42 U.S.C. 262a(a)(1)(B), HHS/CDC 
is seeking comments from the public to provide any information not 
included below to help inform our deliberations regarding 
Staphylococcal enterotoxins:
     The estimated annual number of domestically acquired 
foodborne hospitalization (6% hospitalization rate) and deaths (<0.1% 
death rate) caused by S. aureus is low. (Scallan et al., 2011).
     The ED50 (concentration of a drug that produces 
a biological response) for Staphylococcal enterotoxins:
    [cir] Intravenously: ED50 0.03 [mu]g/kg (rhesus monkeys) 
(Bergdoll, 1979)

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    [cir] Ingestion: ED50 1 [mu]g/kg (rhesus monkeys) 
(Bergdoll, 1979)
    [cir] Intragastrically: ED50 1.7 [mu]g/kg (5 ug/monkey 
for 3 kg rhesus monkeys) (Donnelly et al., 1967)
    Should Staphylococcal enterotoxins be removed or retained as a 
select toxin? If retained, should the Staphylococcal enterotoxins 
exclusion amount be increased or decreased? Please provide a detailed 
explanation for your response.

B. Biological Agents Under Consideration for Being Added to the HHS 
Select Agent and Toxin List

i. New World Hantaviruses
    Some New World Hantaviruses can cause Hantavirus Pulmonary Syndrome 
(HPS) in humans. HPS is an acute febrile illness with a symptoms 
consisting of fever, chills, myalgia, headache, and gastrointestinal 
symptoms (Hooper et al., 2013). Based on the results of the ISATTAC 
evaluation of New World Hantaviruses, HHS/CDC is considering the 
addition of Sin Nombre virus (SNV) and Andes virus to the list of 
select agents because:
     The average case fatality rate in the United States from 
1993 to 2016 is 36% (Centers for Disease Control and Prevention, 2017).
     Andes virus is capable of person-to-person transmission 
(Martinez et al., 2005 and Vitek et al., 1996).
     The infectious and lethal doses are very low. For Andes 
virus in hamsters, the infectious dose is estimated to be between 1-10 
virus particles, and the lethal dose is estimated to be between 10-100 
virus particles (Hooper et al., 2001 and Hooper et al., 2008).
     There are no FDA-approved vaccines or drugs to prevent or 
treat infection with Andes or SNV. Supportive care is the only current 
method of treatment for patients with HPS (Avsic-Zupanc et al., 2019).
    Should Sin Nombre virus and Andes virus be added to the select 
agent list? Should other New World Hantaviruses be regulated as HHS 
select agents? In addition, HHS/CDC is seeking comments regarding the 
potential burden and time needed for an entity possessing SNV or Andes 
virus to come into compliance with the select agents and toxins 
regulatory requirements. Please provide a detailed explanation for your 
response.
ii. Old World Hantaviruses
    Some highly pathogenic Old World Hantaviruses can cause severe 
Hemorrhagic Fever with Renal Syndrome (HFRS). HFRS is a generalized 
infection, and the severity of the disease as well as clinical patterns 
can manifest as mild, moderate or severe disease, depending upon the 
causative virus. HFRS caused by Hantaan and Dobrava viruses is more 
severe, while HFRS caused by Seoul virus is more moderate and by 
Puumala virus is mild (Jonsson et al., 2010). The clinical picture for 
Dobrava virus is severe with more hemorrhagic complications, shock (21 
to 28%), oliguric renal failure (30 to 47%), and abdominal and pleural 
effusions (Maes et al., 2009). Due to the severity of disease with 
Hantaan virus and Dobrava virus, HHS/CDC is considering the addition of 
Hantaan virus and Dobrava virus to the list of select agents because:
     HFRS caused by Hantaan and Dobrava viruses are more severe 
than infection caused by other Old World Hantaviruses such as Seoul, 
Puumala, Sangassou, and Saaremma viruses (Maes et al., 2009 and Avsic-
Zupanc et al., 2019).
     For Hantaan viruses, inhalation infectious dose 
(ID50), is very low and in rats was 0.3-0.7 plaque-forming 
unit (Nuzum et al., 1988).
    Should Hantaan virus and Dobrava virus be added to the select agent 
list? Should other Old World Hantaviruses be regulated as select 
agents? In addition, HHS/CDC is seeking comments regarding the 
potential burden and time needed for an entity possessing the Hantaan 
or Dobrava virus to come into compliance with the select agents and 
toxins regulatory requirements. Please provide a detailed explanation 
for your response.

C. Exclusion Limits Being Considered for the Following Toxins

    Based on the criteria for listing select toxins specified under 42 
U.S.C. 262a(a)(1)(B), HHS/CDC is seeking comments from the public to 
provide any information that will help inform our deliberations 
regarding this biennial review including increasing or decreasing the 
exclusion limit for the following toxins:
     Saxitoxin based on the LD50 by ingestion is 
estimated as 0.3-1.0 mg/person (Burrows et al., 1999) and estimated 
mortality rate of 15% for Paralytic Shellfish Poisoning (Rodrique, et 
al., 1990 and Hallegraeff, et al. 1995)
     Tetrodotoxin based on LD50 estimated 15-60 
[mu]g/kg by ingestion (Burrows et al., 1999); 2 [mu]g/kg by inhalation; 
8-14 [mu]g/kg by injection (mouse, dog, rabbit) (Bane et al., 2014) and 
the recent puffer fish poisoning in 2008 Bangladesh involved 141 cases 
with 17 deaths (Islam et al., 2011)
     Botulinum neurotoxin estimated at 1 ug/kg by ingestion; 
0.01-0.012 ug/kg by inhalation; 0.0013-0.0024 ug/kg by injection 
(Guzman et al., 2001)

D. 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 the select agents and toxins list 
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. HHS/CDC is seeking 
public comment on whether Nipah virus should be identified as a Tier 1 
select agent. HHS/CDC is considering whether the Nipah virus should be 
designated as a Tier 1 agent because the public health threat posed by 
Nipah virus is similar to that of Marburg and Ebola viruses which are 
both currently Tier 1, with characteristics such as:
     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 100-10\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 (fever, headache, dizziness, 
vomiting, cough, reduced levels of consciousness, respiratory distress, 
and death) (Hoh et al., 2000; Hossain et al., 2008; and Lo et al., 
2008).
     Severe long-term effects (neurological sequelae including 
encephalopathy, cranial nerve palsies, and dystonia) (Sejvar et al., 
2007 and Lo et al., 2008). For entities that are currently registered 
to possess Nipah virus, they are also in possession of other Tier 1 
select agents. Therefore, designating Nipah virus as Tier 1 select 
agent would not require an entity to meet additional requirements 
associated with Tier 1 agents. Should Nipah virus be identified as a 
Tier 1 select agent? Please provide a detailed explanation for your 
response.

V. References

Arnon, S.S., et al., Botulinum toxin as a biological weapon: Medical 
and public health management. JAMA, 2001. 285(8): p. 1059-70.

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Avsic-Zupanc T., et al. M. Hantavirus Infections, Clin Micro and 
Infect. 2019. p. e1-11.
Bane, V., et al., Tetrodotoxin: chemistry, toxicity, source, 
distribution and detection. Toxins, 2014. 6(2): p. 693-755.
Bergdoll, M.S. Staphylococcal intoxications. in Foodborne infections 
and intoxications, 2nd Edition, H. Riemann and F.L. Bryan, Ed. 1979, 
Academic Press.
Bovarnick, M., et al. The Influence of Certain Salts, Amino Acids, 
Augars, and Proteins on the Stability of Rickettsiae. J Bacteriol. 
1950. 59(4): p. 509-22.
Bulaj G., et al. Folding of Conotoxins: Formation of the Native 
Disulfide Bridges During Chemical Synthesis and Biosynthesis of 
Conus Peptides. Antioxid Redox Signal, 2008. 10(1):p. 141-55.
Burrows, W.D., et al. Biological warfare agents as threats to 
potable water. Environ Health Perspect, 1999. 107(12): p. 975-84.
Centers for Disease Control and Prevention. 2017. Annual U.S. 
Hantavirus Disease and HPS Case Fatality, 1993-2016. Retrieved from 
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11(9): p. 3537-53.

    Dated: February 21, 2020.
Alex M. Azar II,
Secretary.
[FR Doc. 2020-05477 Filed 3-16-20; 8:45 am]
 BILLING CODE 4163-18-P