[Federal Register: October 16, 2008 (Volume 73, Number 201)]
[Rules and Regulations]
[Page 61363-61366]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16oc08-15]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
42 CFR Part 73
RIN 0920-AA09
Possession, Use, and Transfer of Select Agents and Toxins
AGENCY: Centers for Disease Control and Prevention (CDC), Department of
Health and Human Services (HHS).
ACTION: Final rule.
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SUMMARY: This document completes the biennial review and republication
of the lists of biological agents and toxins regulated by the U.S.
Department of Health and Human Services (HHS), as well as those
biological agents and toxins regulated by both HHS and the U.S.
Department of Agriculture (USDA). Because USDA has chosen to no longer
regulate ten biological agents and toxins which HHS still believes have
the potential to pose a severe threat to public health and safety, we
have moved those ten biological agents and toxins from the overlap
select agents and toxins section to the HHS select agents and toxins
section of the select agent regulations.
In a companion document published in this issue of the Federal
Register, the USDA has established corresponding final rules regarding
the select agents and toxins regulated only by the USDA, as well as
those overlap select agents and toxins regulated by both agencies.
DATES: The final rule is effective November 17, 2008.
FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of
Select Agents and Toxins, Centers for Disease Control and Prevention,
1600 Clifton Rd., MS A-46, Atlanta, GA 30333. Telephone: (404) 718-
2000.
SUPPLEMENTARY INFORMATION: The Public Health Security and Bioterrorism
Preparedness and Response Act of 2002, Subtitle A of Public Law 107-188
(42 U.S.C. 262a) (the Bioterrorism Preparedness Act), requires the HHS
Secretary to establish by regulation a list of each biological agent
and each toxin that has the potential to pose a severe threat to public
health and safety. In determining whether to include an agent or toxin
on the list, the HHS Secretary considers 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; the potential for an agent or toxin to be used as a biological
weapon; and the needs of children and other vulnerable populations. The
Bioterrorism Preparedness Act requires that the HHS Secretary review
and republish the list of select agents and toxins on at least a
biennial basis.
The HHS Secretary promulgated the current select agents and toxins
lists in a final rule, published on March 18, 2005, and made effective
on April 18, 2005. The select agents and toxins lists found in Part 73
are found in two sections. The biological agents and toxins listed in
section 73.3 (HHS select agents and toxins) are those biological agents
and toxins regulated only by HHS. The biological agents and toxins
listed in section 73.4 (Overlap select agents and toxins) are those
biological agents and toxins regulated both by HHS and USDA under the
provisions of the Agricultural Bioterrorism Protection Act of 2002.
The Agricultural Bioterrorism Protection Act of 2002, Subtitle B of
Public Law 107-188 (7 U.S.C. 8401) (the Agricultural Bioterrorism
Protection Act), requires the USDA Secretary to establish by regulation
a list of each biological agent and each toxin that the Secretary
determines has the potential to pose a severe threat to animal or plant
health or animal or plant products. In determining whether to include
an agent or toxin on the list, the USDA Secretary considers the effect
of exposure to the agent or toxin on animal or plant health, and on the
production and marketability of animal or plant products; the
pathogenicity of the agent or the toxicity of the toxin and the methods
by which the agent or toxin is transferred to animals and plants; the
availability and effectiveness of pharmacotherapies and prophylaxis to
treat and prevent any illness caused by the agent or toxin; and the
potential of an agent or toxin for use as a biological weapon. The USDA
Secretary is also required to conduct a biennial review of the USDA
select agents and toxins list.
To assist with the biennial review, HHS reviewed recommendations
provided by subject matter experts and the Intragovernmental Select
Agents and
[[Page 61364]]
Toxins Technical Advisory Committee (ISATTAC). The ISATTAC is comprised
of Federal government employees from the CDC, the National Institutes
of Health (NIH), the Food and Drug Administration (FDA), the USDA/
Animal and Plant Health Inspection Service (APHIS), USDA/Agricultural
Research Service (ARS), USDA/CVB (Center for Veterinary Biologics) and
the Department of Defense (DOD).
HHS completed its biennial review on February 22, 2007 and on
August 28, 2007, we published in the Federal Register (72 FR 49244) a
proposal to neither add nor remove any agents or toxins from our select
agents and toxins lists. However, we did advise that HHS intended to
continue to regulate ten biological agents and toxins that USDA was
proposing to no longer regulate.
After conducting its biennial review, on August, 28, 2007 (72 FR
49231) USDA proposed that it would no longer regulate ten of the
biological agents and toxins currently listed by them as ``overlap''
select agents and toxins. Published in today's Federal Register is
USDA's final rule that removes from Part 121 of Title 9 of the Code of
Federal Regulations the following agents and toxins: Botulinum
neurotoxins, Botulinum neurotoxin producing species of Clostridium,
Coxiella burnetti, Francisella tularensis, Coccidioides immitis,
Eastern equine encephalitis virus, T-2 toxin, Staphylococcal
enterotoxins, Shigatoxin, and Clostridium perfringens epsilon toxin.
For the proposed rule, we provided for a 60-day comment period for
written comments that ended October 29, 2007. Relevant issues raised by
the comments are discussed below. Based on the rationale set forth in
the proposed rule, we are affirming the provisions of the proposed rule
as a final rule.
Commenters recommended that the following biological agents and
toxins be removed from the HHS list to mirror their removal by USDA:
(1) Botulinum neurotoxin producing species of Clostridium, (2) Eastern
equine encephalitis virus, (3) Botulinum neurotoxins; and (4)
Clostridium perfringens epsilon toxin because ``they are found
naturally in the U.S. and most are ubiquitous and the proposed rule
does not give the basis for maintaining these naturally occurring
agents.'' One commenter further argued that Clostridium perfringens
epsilon toxin should be removed because ``the use of this toxin as a
bioterrorism weapon is highly unlikely due to several factors including
the method and effectiveness of administration, the lack of potential
secondary transmission to uninfected individuals.'' We made no changes
based on these comments. The potential negative impact of exposure to a
select agent or toxin to the public health may be different from its
impact on agriculture. As a part of its review using subject matter
experts, HHS determines whether a select agent or toxin has the
potential to pose a significant public health threat based on the
effect of the exposure to the agent or toxin to humans, the degree of
contagiousness that an agent will have with respect to humans,
availability of treatments for humans, and the susceptibility by
vulnerable human populations. Based on these criteria, HHS confirmed
its prior determination that these agents and toxins have the potential
to pose a significant public health threat because they have acute
toxicity, have lethality in humans, can easily be produced in large
quantities, and can be transferred by an aerosol method. In contrast,
USDA's evaluations and determinations that it would remove these agents
and toxins from its regulation is detailed in their Federal Register
notice published on August 28, 2007 (See 72 FR 49231) and today's
Federal Register that:
Botulinum neurotoxin producing species of Clostridium
(i.e., C. botulinum, C. butyricum and C. baratii) are widely
distributed in soil, sediments of lakes and ponds, and decaying
vegetation. The species may be found in any region of the world and
some species may occasionally colonize the intestinal tract of birds
and mammals under natural conditions. The neurotoxins produced by these
agents produce the infectious toxicosis of botulism. There is a well
known and established history of infection and toxicosis in
agricultural species associated with C. botulinum in the United States,
and UDSA concluded that Botulinum neurotoxin producing species do not
pose a serious threat to American agriculture.
Based on evidence that transmissibility from animal to
animal is negligible and that, historically, outbreaks of botulism
occur periodically in the United States, USDA determined that botulinum
neurotoxins are a poor agroterrorism weapon, and USDA should therefore
remove Botulinum neurotoxins and Botulinum neurotoxin producing species
of Clostridium from the list of overlap select agents in its
regulations in Sec. 121.4(b).
Eastern equine encephalitis virus has been recognized as
an important veterinary pathogen that infects equines and birds during
sporadic outbreaks. Infection results in central nervous system
dysfunction and may result in moderate to high morbidity and mortality.
The virus is maintained naturally in nature in marshes and swamps in an
enzootic bird-mosquito-bird cycle, and is endemic in the United States
along the Atlantic and Gulf coasts. Eastern equine encephalitis virus
does not play a major role in agricultural species of concern, and
equine species are considered a dead-end host of the virus.
Additionally, the working group concluded that because the
following overlap select agents and toxins are naturally found in the
United States, do not pose a significant impact to animal health, and
are not likely candidates for use in an agroterrorism event directed
toward animal health, these select agents and toxins would have a
limited socio-economic impact on American agriculture, and thus should
be removed from the list: Botulinum neurotoxin producing species of
Clostridium, Clostridium perfringens epsilon toxin, Francisella
tularensis, Staphylococcal enterotoxin, shigatoxin, and T-2 toxin.
One commenter further proposed that (1) ``CDC provides an exemption
for the use of the agents noted above in the manufacture of veterinary
biologics in facilities licensed by the USDA's Center for Veterinary
Biologics (CVB) or their investigational use by biologics firms under
CVB supervision,'' (2) ``that they remain on the overlap list'' or (3)
``if they remain on the CDC Select Agent list and are removed from the
Overlap list that CDC utilize the CVB for oversight and inspection of
CVB licensed firms.'' We made no changes based on these comments. The
regulations currently provide that products that are, bear, or contain
listed select agents or toxins that are cleared, approved, licensed, or
registered under the Virus-Serum-Toxin Act (21 U.S.C. 151-159) are
exempt from the provisions of this part insofar as their use meets the
requirements of that Act. Veterinary biologics licensed by USDA's
Center for Veterinary Biologics are licensed under the authority of the
Virus-Serum-Toxin Act. The regulations also provide that on a case-by-
case basis the HHS Secretary may exempt from the requirements of the
part 73 regulations an investigational product that is, bears, or
contains a select agent or toxin, when such product is being used in an
investigation authorized under any Federal Act and additional
regulation under part 73 is not necessary to protect public health and
safety. See 42 CFR 73.5(d). While we and USDA do everything we can to
minimize disruption due to select agent oversight, CDC has determined
that it would not be appropriate to utilize CVB for oversight and
inspection of registered
[[Page 61365]]
entities that only have select agents and toxins on the HHS list.
Several commenters noted a typographical error on page 49245 that
listed the aggregate amount for Botulinum neurotoxins as ``05. mg.''
This was a typographical error and we were not proposing to change the
aggregate amount for Botulinum neurotoxins under the control of a
principal investigator, a treating physician or veterinarian, or a
commercial manufacturer or distributor that would meet the exclusion
provisions for part 73. The maximum aggregate amount of Botulinum
neurotoxins under the control of a principal investigator, a treating
physician or veterinarian, or a commercial manufacturer or distributor
that meets the requirement for exclusion under 42 CFR 73.4 will
continue to be 0.5 mg.
Regulatory Analyses
Paperwork Reduction Act
The Paperwork Reduction Act of 1995 (44 U.S.C. 3507(d)) requires
that the HHS consider the impact of paperwork and other information
collection burdens imposed on the public. We have determined no new
information collection requirements are associated with this proposed
rule.
Executive Order 12866 and Regulatory Flexibility Act
This final rule has been reviewed under Executive Order 12866, and
has been determined not to be significant. For this action, the Office
of Management and Budget has waived its review under Executive Order
12866.
The Regulatory Flexibility Act (5 U.S.C. 601 et seq.) requires an
agency to review regulations to assess their impact on small entities
unless the agency determines that a rule is not expected to have a
significant impact on a substantial number of small entities. This rule
will have no costs because it merely changes the designation of ten
select agents and toxins from being regulated by both HHS and USDA to
being regulated solely by HHS. We hereby certify this proposed rule
will not have a significant economic impact on a substantial number of
small businesses.
Unfunded Mandates
The Unfunded Mandates Reform Act at 2 U.S.C. 1532 requires that
agencies prepare an assessment of anticipated costs and benefits before
developing any rule that may result in expenditure by State, local, or
tribal governments, in the aggregate, or by the private sector of $100
million or more (adjusted for inflation) in any given year. This
proposed rule is not expected to result in any one-year expenditure
that would exceed this amount.
Executive Order 12988
This Final Rule has been reviewed under Executive Order 12988,
Civil Justice Reform. This rule: (1) Would preempt all State and local
laws and regulations that are inconsistent with this rule; (2) would
have no retroactive effect; and (3) would not require administrative
proceedings before parties may file suit in court challenging this
rule.
Executive Order 13132
This Final Rule has been reviewed under Executive Order 13132,
Federalism. The notice does not propose any regulation that would
preempt State, local, and Indian tribe requirements, or that would have
any 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.
List of Subjects in 42 CFR Part 73
Biologics, Incorporation by reference, Packaging and containers,
Penalties, Reporting and recordkeeping requirements, Transportation.
Dated: September 22, 2008.
Michael O. Leavitt,
Secretary.
0
For the reasons stated in the preamble, we have amended 42 CFR part 73
as follows:
PART 73--SELECT AGENTS AND TOXINS
0
1. The authority citation for part 73 continues to read as follows:
Authority: 42 U.S.C. 262a; sections 201-204, 221 and 231 of
Title II of Public Law 107-188, 116 Stat. 637 (42 U.S.C. 262a).
0
2. In Sec. 73.3, revise paragraphs (b), (d)(3), and (f)(3)(i) to read
as follows:
Sec. 73.3 HHS select agents and toxins.
* * * * *
(b) HHS select agents and toxins:
Abrin
Botulinum neurotoxins
Botulinum neurotoxin producing species of Clostridium
Cercopithecine herpesvirus 1 (Herpes B virus)
Clostridium perfringens epsilon toxin
Coccidioides posadasii/Coccidioides immitis
Conotoxins
Coxiella burnetii
Crimean-Congo haemorrhagic fever virus
Diacetoxyscirpenol
Eastern Equine Encephalitis virus
Ebola viruses
Francisella tularensis
Lassa fever virus
Marburg virus
Monkeypox virus
Ricin
Rickettsia prowazekii
Rickettsia rickettsii
Saxitoxin
Shiga-like ribosome inactivating proteins
Shigatoxin
South American Haemorrhagic Fever viruses (Junin, Machupo, Sabia,
Flexal, Guanarito)
Staphylococcal enterotoxins
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis complex (flavi) viruses (Central European Tick-
borne encephalitis, Far Eastern Tick-borne encephalitis [Russian Spring
and Summer encephalitis, Kyasanur Forest disease, Omsk Hemorrhagic
Fever])
Variola major virus (Smallpox virus) and Variola minor virus (Alastrim)
Yersinia pestis
* * * * *
(d) * * *
(3) HHS toxins under the control of a principal investigator,
treating physician or veterinarian, or commercial manufacturer or
distributor, if the aggregate amount does not, at any time, exceed the
following amounts: 100 mg of Abrin; 0.5 mg of Botulinum neurotoxins;
100 mg of Clostridium perfringens epsilon toxin; 100 mg of Conotoxins;
1,000 mg of Diacetoxyscirpenol; 100 mg of Ricin; 100 mg of Saxitoxin;
100 mg of Shiga-like ribosome inactivating proteins; 100 mg of
Shigatoxin; 5 mg of Staphylococcal enterotoxins; 1,000 mg of T-2 toxin;
or 100 mg of Tetrodotoxin.
* * * * *
(f) * * *
(3) * * *
(i) The seizure of Botulinum neurotoxins, Ebola viruses,
Francisella tularensis, Lassa fever virus, Marburg virus, South
American Haemorrhagic Fever virus (Junin, Machupo, Sabia, Flexal,
Guanarito), Variola major virus (Smallpox virus), Variola minor
(Alastrim), or Yersinia pestis must be reported within 24 hours by
telephone, facsimile, or e-mail. This report must be followed by
submission of APHIS/CDC Form 4 within seven calendar days after seizure
of the select agent or toxin.
* * * * *
[[Page 61366]]
0
3. In Sec. 73.4, revise paragraphs (b) and (f)(3)(i), and remove
paragraph (d)(3) to read as follows:
Sec. 73.4 Overlap select agents and toxins.
* * * * *
(b) Overlap select agents and toxins:
Bacillus anthracis
Brucella abortus
Brucella melitensis
Brucella suis
Burkholderia mallei (formerly Pseudomonas mallei)
Burkholderia pseudomallei (formerly Pseudomonas pseudomallei)
Hendra virus
Nipah virus
Rift Valley fever virus
Venezuelan Equine Encephalitis virus
* * * * *
(f) * * *
(3) * * *
(i) The seizure of Bacillus anthracis, Brucella melitensis, Hendra
virus, Nipah virus, Rift Valley fever virus, or Venezuelan equine
encephalitis virus must be reported within 24 hours by telephone,
facsimile, or e-mail. This report must be followed by submission of
APHIS/CDC Form 4 within seven calendar days after seizure of the select
agent or toxin.
* * * * *
0
4. In Sec. 73.5 revise paragraph (a)(3)(i) to read as follows:
Sec. 73.5 Exemptions for HHS select agents and toxins.
(a) * * *
(3) * * *
(i) The identification of any of the following HHS select agents or
toxins must be immediately reported by telephone, facsimile, or e-mail:
Botulinum neurotoxins, Ebola viruses, Francisella tularensis, Lassa
fever virus, Marburg virus, South American Haemorrhagic Fever viruses
(Junin, Machupo, Sabia, Flexal, Guanarito), Variola major virus
(Smallpox virus), Variola minor (Alastrim), or Yersinia pestis. This
report must be followed by submission of APHIS/CDC Form 4 within seven
calendar days after identification.
* * * * *
0
5. In Sec. 73.6, revise paragraph (a)(3)(i) to read as follows:
Sec. 73.6 Exemptions for overlap select agents and toxins.
(a) * * *
(3) * * *
(i) The identification of any of the following overlap select
agents or toxins must be immediately reported by telephone, facsimile,
or e-mail: Bacillus anthracis, Brucella melitensis, Hendra virus, Nipah
virus, Rift Valley fever virus, or Venezuelan equine encephalitis
virus. This report must be followed by submission of APHIS/CDC Form 4
within seven calendar days after identification.
* * * * *
[FR Doc. E8-24623 Filed 10-15-08; 8:45 am]
BILLING CODE 4163-18-P
