[Federal Register Volume 77, Number 194 (Friday, October 5, 2012)]
[Rules and Regulations]
[Pages 61084-61115]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-24389]
[[Page 61083]]
Vol. 77
Friday,
No. 194
October 5, 2012
Part III
Department of Health and Human Services
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42 CFR Part 73
Possession, Use, and Transfer of Select Agents and Toxins; Biennial
Review; Final Rule
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules
and Regulations
[[Page 61084]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. CDC-2011-0012]
42 CFR Part 73
RIN 0920-AA34
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: Final rule.
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SUMMARY: In accordance with the Public Health Security and Bioterrorism
Preparedness and Response Act of 2002, the Centers for Disease Control
and Prevention (CDC) located within the Department of Health and Human
Services (HHS) has reviewed the list of biological agents and toxins
that have the potential to pose a severe threat to public health and
safety and is republishing that list. As a result of our review, we
have added Chapare virus, Lujo virus, and SARS-associated coronavirus
(SARS-CoV) to the list of HHS select agents and toxins. We have also
removed from the list of HHS and overlap select agents and toxins, or
excluded from compliance with part 73, the agents and toxins described
in the Executive Summary. Further, in accordance with Executive Order
13546, ``Optimizing the Security of Biological Select Agents and Toxins
in the United States,'' HHS/CDC has designated those 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 as ``Tier
1'' agents; established new security requirements for entities
possessing Tier 1 agents, including the requirement to conduct pre-
access assessments and on-going monitoring of personnel with access to
Tier 1 agents and toxins; and made revisions to the regulations to
clarify regulatory language concerning security, training, biosafety,
and incident response.
In a companion document published in this issue of the Federal
Register, the United States Department of Agriculture (USDA) has made
parallel regulatory changes.
DATES: Effective Dates: The amendments to Sec. Sec. 73.1, 73.3 through
73.6, 73.9, 73.10, 73.13, 73.16, 73.17, and 73.20, of Title 42, Code of
Federal Regulations are effective December 4, 2012. The remaining
provisions to this final rule are effective April 3, 2013.
Applicability Dates: By December 4, 2012, all entities that possess
SARS, Chapare, and Lujo viruses must provide notice to CDC regarding
their possession of these viruses, and by April 3, 2013, all previously
unregistered entities must meet all of the requirements of this part.
The Final Rule timelines are based on the timelines that worked
effectively for the Federal Select Agent Program Interim Final Rules
that were published in December 2002. If the regulated community has
concerns about the established timeline, they can contact Federal
Select Agent Program for technical assistance.
Comment Date: Written comments on the new information collection
contained in this final rule should be received by October 15, 2012.
ADDRESSES: Please send written comments on the new information
collection contained in this final rule to CDC Desk Officer, Office of
Management and Budget, Washington, DC 20503 or by fax to (202) 395-
5806.
FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of
Select Agents and Toxins, Centers for Disease Control and Prevention,
1600 Clifton Road NE., Mailstop A-46, Atlanta, Georgia 30333.
Telephone: (404) 718-2000.
SUPPLEMENTARY INFORMATION: The Preamble to this final rule is organized
as follows:
I. Executive Summary
II. Changes to 42 CFR Part 73
A. Modifications to the List of HHS and Overlap Select Agents
and Toxins
B. Tiering of Select Agents and Toxins
C. Responses to Other Proposed Changes
i. Definitions
ii. Exclusions
iii. Toxins
iv. Exemptions
v. Responsible Official
vi. Access to Select Agents and Toxins
vii. Security
viii. Security for Tier 1 Agents and Toxins
ix. Biosafety Plan
x. Restricted Experiments
xi. Incident Response
xii. Training
xiii. Transfers
xiv. Records
xv. Administrative Review
xvi. Guidance Documents
xvii. Miscellaneous
III. Required Regulatory Analyses
A. Executive Orders 12866 and 13563
B. Regulatory Flexibility Act
C. Paperwork Reduction Act of 1995
D. Executive Order 12988: Civil Justice Reform
E. Executive Order 13132: Federalism
F. Plain Writing Act of 2010
IV. References
I. Executive Summary
We published an Advance Notice of Proposed Rulemaking (ANPRM) (75
FR 42363) on July 21, 2010 and a Notice of Proposed Rulemaking (NPRM)
(76 FR 61206) on October 3, 2011. The NPRM solicited comments regarding
(1) the appropriateness of the current HHS list of select agents and
toxins; (2) whether there are other biological agents or toxins that
should be added to the HHS list; (3) whether biological agents or
toxins currently on the HHS list should be deleted from the list; (4)
whether the HHS select agents and toxins list should be tiered based on
the relative bioterrorism risk of each biological agent or toxin; and
(5) whether the security requirements for select agents or toxins in
the highest tier should be further stratified based on type of use or
other factors. In addition, Executive Order 13546 ``Optimizing the
Security of Biological Select Agents and Toxins in the United States''
directed the HHS Secretary to (1) designate a subset of the select
agents and toxins list (Tier 1) that presents 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; (2) explore options for graded
protection for these Tier 1 agents and toxins to permit tailored risk
management practices based upon relevant contextual factors; and (3)
consider reducing the overall number of agents and toxins on the select
agents and toxins list.
We provided a 60-day comment period for written comments that ended
December 2, 2011. We extended the comment period for an additional 30-
day period that ended January 17, 2012.
The changes to the current regulations include:
1. Modification of the select agent and toxin list:
a. The following viruses are added to the HHS select agent list
based on scientific data related to their significant public health
risk: SARS-CoV, Lujo and Chapare viruses.
b. The following agents would no longer be considered HHS select
agents or toxins, or would be excluded from compliance with part 73:
Cercopithecine Herpesvirus 1 (Herpes B virus), Clostridium perfringens
epsilon toxin, Coccidioides posadasii/Coccidioides immitis, Eastern
Equine Encephalitis virus (South American type only), Flexal virus,
West African clade of Monkeypox virus, Rickettsia rickettsii, the non-
short, paralytic alpha conotoxins containing the following amino acid
sequence
[[Page 61085]]
X1CCX2PACGX3X4X5X
6CX7, \1\ Shigatoxins, Shiga-like ribosome
inactivating proteins, Staphylococcal Enterotoxins (non-A, non-B, non-
C, non-D, and non-E subtypes), and Tick-borne encephalitis complex
viruses (Central European subtype).
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\1\ C = Cysteine residues (indicated in bold) 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 [alpha]-MI and [alpha]-GI (shown above) as
well as [alpha]-GIA, Ac1.1a, [alpha]-CnIA, [alpha]-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.
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c. The following agent would no longer be considered an overlap
select agent: Venezuelan Equine Encephalitis Virus (subtypes ID and
IE).
2. Tiering of the select agent and toxin list:
a. Tier I agents:
i. HHS select agents and toxins
(1) Ebola virus
(2) Francisella tularensis
(3) Marburg virus
(4) Variola major virus
(5) Variola minor virus
(6) Yersinia pestis
(7) Botulinum neurotoxin
(8) Botulinum neurotoxin producing species of Clostridium
ii. Overlap select agents and toxins
(1) Bacillus anthracis
(2) Burkholderia mallei
(3) Burkholderia pseudomallei
3. Establishing physical security standards for entities possessing
Tier I select agents and toxins, including the requirement to conduct
pre-access assessments and on-going monitoring of personnel with access
to Tier 1 agents and toxins;
4. Miscellaneous revisions to the regulations to clarify regulatory
language concerning security, training, biosafety, and incident
response.
Costs of the Rule: The entities that will be affected by the final
rules include research and diagnostic facilities; Federal, State, and
university laboratories; and private commercial and non-profit
enterprises. The regulations require registering the possession, use,
and transfer of select agents or toxins. In addition, the entity is
required to ensure that the facility where the agent or toxin is housed
has adequate biosafety and containment measures, that the physical
security of the premises is adequate, that all individuals with access
to select agents or toxins have the appropriate education, training,
and/or experience to handle such agents or toxins, and that complete
records concerning activities related to the select agents or toxins
are maintained.
The final rules will further reduce or minimize the risk of misuse
of select agents and toxins that have the potential to pose a severe
threat to human, animal or plant health, or to animal or plant
products. The USDA/Animal and Plant Health Inspection Service (APHIS)
and HHS/CDC recognize that several of the required measures of the
regulations may impose certain operational costs upon affected
entities, particularly entities that have the newly designated Tier 1
select agents and toxins. In many cases, however, the affected entities
already employ some or all of the required measures. Compliance costs
actually incurred will therefore vary from one entity to the next.
While information on the specific changes that would need to occur
at individual sites and the associated costs was not readily available
during proposed rulemaking, some general observations regarding the
potential costs were presented. These general cost observations can be
found in table 2 in the Regulatory Impact Analysis located at:
www.regulations.gov and at http://www.selectagents.gov/.
Benefits of the Rule: The objectives of the final rules are to
create a means of ensuring enhanced oversight in the transfer, storage,
and use of select agents and toxins; define the security procedures and
suitability assessments for pre-access suitability and continual
monitoring of individuals with access to Tier 1 select agents and
toxins; and require that entities in possession of such agents and
toxins develop and implement effective means of biosafety, information
security, and physical security. The overall benefit of the amended
provisions will be a reduced likelihood of the accidental or
intentional release of a select agent or toxin and the avoidance of
costs associated with such a release. The goal of the amended
regulations is to enhance the protection of human, animal, and plant
health and safety.
II. Changes to 42 CFR Part 73
The table below describes the changes to the current regulation.
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Section No. Current Change
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73.0..................... Applicability and No change.
related
requirements.
73.1..................... Definitions........ Definitions added:
Conotoxins; Information
security; Occupational
exposure; Recombinant
nucleic acids; Security
barrier; and Synthetic
nucleic acids.
73.2..................... Purpose and scope.. No change.
73.3..................... HHS select agents Designates Tier 1 select
and toxins. agents and toxins; adds
select agents and
toxins; clarifies
language; deletes from
the HHS list.
73.4..................... Overlap select Designates Tier 1 select
agents and toxins. agents and toxins; adds
select agents and
toxins; clarifies
language; deletes from
the overlap list.
73.5..................... Exemptions for HHS Amends the immediate
select agents and notification list to
toxins. Tier 1 agents;
clarifies language.
73.6..................... Exemptions for Amends the immediate
overlap select notification list to
agents and toxins. Tier 1 agents;
clarifies language.
73.7..................... Registration and No change.
related security
risk assessments.
73.8..................... Denial, revocation, No change.
or suspension of
registration.
73.9..................... Responsible Adds new paragraph
Official. (a)(5); clarifies
language.
73.10.................... Restricting access Adds new paragraph (e);
to select agents adds clarifying
and toxins; language.
security risk
assessments.
73.11.................... Security........... Revises regulatory text--
paragraph (b),
(c)(2),(g). Adds new
paragraphs (c)(8),
(c)(9), (c)(10), (e),
(f).
73.12.................... Biosafety.......... Revises paragraphs (a)
and (c)(1); replaces
``url'' in paragraph
(c)(3); adds new
paragraph (d).
[[Page 61086]]
73.13.................... Restricted Clarifies language.
experiments.
73.14.................... Incident response.. Revises paragraphs (a),
(b); adds new
paragraphs (c) and (e).
73.15.................... Training........... Revises paragraph (a);
redesignates and
revises paragraphs (b),
(c); adds new paragraph
(b).
73.16.................... Transfers.......... Redesignates paragraphs;
adds new paragraphs
(f), (h), (l).
73.17.................... Records............ Revises paragraph
(a)(1); adds new
paragraph (a)(2).
73.18.................... Inspections........ No changes.
73.19.................... Notification of No changes.
theft, loss, or
release.
73.20.................... Administrative Revises paragraphs.
review.
73.21.................... Civil money No changes.
penalties.
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A. Modifications to the List of HHS and Overlap Select Agents and
Toxins
The changes to the list of HHS select agents and toxins are based
on comments received in response to the NPRM, recommendations from the
Federal Experts Security Advisory Panel (FESAP) and HHS/CDC's
Intragovernmental Select Agents and Toxins Technical Advisory Committee
(ISATTAC), and our review of current scientific literature.
Executive Order 13546 established the FESAP to advise the HHS
Secretary on the designation of Tier 1 agents and toxins, the reduction
in the number of agents on the select agent list, the establishment of
appropriate practices to ensure reliability of personnel with access to
Tier 1 agents, and the establishment of the appropriate practices for
physical security and cyber security for facilities that possess Tier 1
agents.
The ISATTAC was established by the CDC Director and is comprised of
Federal government employees from the CDC, the National Institutes of
Health (NIH), the Food and Drug Administration (FDA), the Biomedical
Advanced Research and Development Authority (BARDA) within the HHS
Office of the Assistant Secretary for Preparedness and Response (HHS/
ASPR), the USDA/APHIS, USDA/Agricultural Research Service (ARS), USDA/
CVB (Center for Veterinary Biologics), the Department of Homeland
Security (DHS), and the Department of Defense (DOD). The purpose of the
ISATTAC is to assist CDC's Division of Select Agents and Toxins in
performing its regulatory functions under the select agent regulations,
including conducting a review of the select agents and toxins list.
We received 113 comments that addressed the composition of the
select agents and toxins list.
As discussed below, the final rule removes or excludes 13 select
agents and toxins, added 3 select agents, and designated 11 select
agents and toxins as ``Tier 1'' agents.
HHS Select Agents and Toxins
Addition of Chapare and Lujo Viruses
On August 19, 2009, we proposed adding the haemorrhagic fever virus
Chapare, to the list of select agents (74 FR 41829). Chapare virus is a
recently described New World arenavirus that is associated with fatal
hemorrhagic fever syndrome and is most closely related to Sabia virus,
an HHS select agent (Ref 1).
On October 3, 2011, we proposed adding the haemorrhagic fever virus
Lujo to the list of select agents (76 FR 61206). According to available
reports, Lujo virus (1) caused a fatal outbreak of hemorrhagic fever,
(2) has a case fatality rate of 80 percent, (3) has been
phylogenetically identified as an arenavirus, and (4) is related to
those members of the Old World arenaviridae family (Junin, Machupo,
Sabia, Guanarito, and Lassa) listed as HHS select agents that cause
hemorrhagic fever and pose a significant risk to public health and
safety (Ref 2).
Some commenters argued that there does not appear to be valid
evidence that these viruses could be effectively utilized as terrorism
agents. Another commenter recommended that all hemorrhagic arenaviruses
be included in the select agent list.
We made no changes to the HHS list of select agents and toxins
based on these comments. Although the literature on these newly
described viruses is small and recent, both viruses have thus far
produced high morbidity and mortality rates. Both Lujo and Chapare
virus share other characteristics with regulated hemorrhagic fever
viruses (Junin, Machupo, Sabia, Guanarito, and Lassa). As a taxonomic
group, the hemorrhagic arenaviruses exhibit distinct differences in
morbidity, mortality, transmissibility, and degree of pathogenicity.
Therefore our consideration of whether to add a particular arenavirus
to the list is made on a taxon-by-taxon basis. As more information
becomes known about the public health risks of these two new
hemorrhagic fever viruses, their status as select agents can be
reassessed.
Individuals and entities that currently possess Chapare or Lujo
virus, if they are not already registered entities, will have to either
transfer the organism or genomic material to a registered entity,
destroy their stocks and report the destruction to HHS/CDC, or if they
choose to retain their stocks, register with HHS/CDC and comply with
all applicable regulations as provided in this final rule. We also
recognize that those entities that choose to become registered will
need time to come into full compliance with the requirements of the
regulations. This final rule will become effective on December 4, 2012.
On and after that date, any individual or entity possessing, using, or
transferring any listed select agent or toxin must be in compliance
with the provisions of each part. However, to minimize the disruption
of critical research or educational projects involving Chapare or Lujo
virus that are underway as of the effective date of these regulations,
we are providing that any individual or entity possessing Chapare or
Lujo virus as of the effective date (current possessors) will be
afforded additional time to reach full compliance with the regulations
in each part. Accordingly, by December 4, 2012, all entities that
possess Chapare and/or Lujo virus must provide notice to HHS/CDC
regarding their possession of Chapare and/or Lujo virus, and by April
3, 2013, all previously unregistered entities must meet all of the
requirements of this part.
Addition of SARS-Associated Coronavirus (SARS-CoV)
SARS-CoV is associated with one of the most significant pandemics
of the 21st century. According to the World Health Organization, the
2002-2003 SARS pandemic involved 29 countries, produced over 8000 cases
of disease, and resulted in 774 deaths (Ref 3). Since the end of the
pandemic the majority of reported SARS-CoV infections have occurred in
laboratorians, or individuals who had close contact with infected
laboratorians (Ref 4-6). At least 13 (6 primary cases and 7 contacts)
[[Page 61087]]
individuals have contracted laboratory-associated SARS-CoV infections
(Ref 7).
On July 13, 2009, we proposed the addition of SARS-CoV to the list
of select agents and toxins (74 FR 33401). We received ten comments
from representatives of universities, public health laboratories,
commercial, and government facilities, all arguing that SARS-CoV should
not be added to the select agent list. Commenters believed that further
deliberation of the biosafety and biosecurity issues involved with this
agent should be considered due to the implications for research and
public health activities. The commenters further reasoned that adding
SARS-CoV as a select agent would decrease public safety and security by
preventing expert researchers from pursuing important work due to what
they described as the additional costs and onerous burdens inherent
with the select agent registration and compliance process.
During the public comment period for this rulemaking we received
three comments from representatives from universities and a public
health laboratory that recommended the addition of SARS-CoV to the list
of select agents and toxins because (1) it exhibited high
transmissibility and high lethality; (2) caused epidemics on four
continents with significant mortality; (3) had a major economic impact;
and (4) had a major psychological impact. Commenters further argued
that the virus has demonstrated its ability to cause a contagious
disease, has caused several laboratory infections (including one
incident that led to cases in non-laboratory contacts) and is a virus
which no longer circulates in nature.
We agree with the commenters who supported the addition of SARS-CoV
to the list of select agents and toxins because of the significant
impact of SARS-CoV on the public health system, the high degree of
pathogenicity, and the lack of vaccines or proven therapeutics
currently available to prevent or treat SARS-CoV infections.
Additionally, we note that the virus no longer appears to be naturally
circulating in humans, raising the concern that the general population
does not possess a significant level of immunity.
The genome of SARS-CoV will be regulated as an HHS select agent. As
a member of the Coronarviridae family, SARS-CoV is an enveloped virus
with a positive-sense RNA genome. Positive-sense RNA viruses that
utilize host polymerases contain nucleic acids, in and of themselves,
that can produce infectious forms of the virus. The select agent
regulations apply to nucleic acids that can produce infectious forms of
any of the select agent viruses (See section 3(c) of 42 CFR part 73, 9
CFR part 121, and 7 CFR part 331).
Based on information received from the HHS/CDC's Etiologic Agent
Import Permit Program and the HHS/CDC's Office of Infectious Diseases,
there are 119 entities that currently possess SARS-CoV. Of those 119
entities, 77 entities are registered with the Federal Select Agent
Program; 42 entities are not registered. Of the 42 non-registered
entities, only 38 may possess SARS-CoV or SARS-CoV genomic material
(RNA). The 38 non-registered entities that may possess SARS-CoV or
SARS-CoV genomic material (RNA) include 10 academic, 22 commercial, 5
State government, and 1 Federal government institutions.
Entities and individuals that currently possess SARS-CoV or SARS-
CoV genomic material (RNA) will have to either (1) transfer the
organism or genomic material to a registered entity; (2) destroy their
stocks and report the destruction to CDC; or (3) register with HHS/CDC
or USDA/APHIS to possess SARS-CoV and comply with all applicable
regulations as provided in this final rule. We also recognize that
those entities that choose to become registered with the Federal Select
Agent Program will need time to come into full compliance with the
requirements of the regulations. Since this final rule will become
effective on December 4, 2012 and any individual or entity possessing,
using, or transferring any listed agent or toxin must be in compliance
with the provisions of each part on or after that date, we are
providing that any individual or entity possessing SARS-CoV as of the
effective date (current possessors) will be afforded additional time to
reach full compliance with the regulations in each part. Accordingly,
by December 4, 2012, all entities that possess SARS-CoV must provide
notice to HHS/CDC regarding their possession of SARS-CoV, and by April
3, 2013, all previously unregistered entities must meet all of the
requirements of this part. We are extending the effective date for
these currently non-registered entities to minimize the disruption of
critical research or educational projects involving SARS-CoV that are
underway as of the effective date of these regulations.
Removal of Cercopithecine Herpesvirus 1 (Herpes B Virus)
We are removing Cercopithecine herpesvirus 1 (Herpes B virus) from
the HHS list of select agents and toxins. We proposed the removal of
Cercopithecine herpesvirus 1 (Herpes B virus) from the HHS list of
select agents and toxins because the virus is not easily transmitted to
humans, the person-to-person transmission risk is small, the numbers of
recorded human infections are low, and multiple licensed antiviral
treatments for Herpes B infections are available. The only comments
that we received on this proposal were supportive for the removal.
Removal of Clostridium Perfringens Epsilon Toxin
The proposed rule retained C. perfringens epsilon toxin on the list
of select agents and toxins. The final rule removes it. Commenters
questioned why C. perfringens epsilon toxin was listed as a select
agent since its production is licensed by USDA under the Virus-Serum-
Toxin Act. In addition, commenters argued that from a veterinary
laboratory perspective, C. perfringens epsilon toxin is commonly
detected in the gastrointestinal tract during routine post-mortem
diagnostic testing and the quantity of toxin recovered from a positive
diagnostic sample would be far below the 100 mg exclusion amount
provided for in the select agent regulations. Commenters also supplied
scientific data in support of removal of C. perfringens epsilon toxin
from the select agent and toxin list (Ref 8).
Although many of the concerns raised by the commenters are
addressed by the exemption and exclusion provisions in the regulations
(42 CFR 73.3 and 73.5), we agree with commenters and have determined
that C. perfringens epsilon toxin should be removed from the list of
HHS select agents and toxins. C. perfringens epsilon toxin was
originally included on the select agent list because of its relatively
low (LD)50 (lethal dose fifty: the amount of the toxin
required to kill 50 percent of the test population) in rodents and
moderate toxicity when in aerosol form. The LD50 results for
C. perfringens epsilon toxin are based on a mouse in vivo injection
model, which does not completely mimic a natural infection, and
therefore may not accurately represent the human LD50.
Additional significant factors in our determination to remove C.
perfringens epsilon toxin include the absence of known human cases of
disease, a lack of human or non-human primate toxicity data, and
insufficient new data to indicate that C. perfringens epsilon toxin is
a significant threat to public health and safety.
Reduction of Conotoxins on the HHS List of Select Agents and Toxins
The term ``conotoxin'' is used broadly to comprise a very large
number of polypeptides isolated from the venom of
[[Page 61088]]
fish-hunting marine snails of the Conus genus of gastropod mollusks.
Many of these molecules are neurologically active in mammals. Although
we did not propose the removal for conotoxins, we did receive multiple
comments that conotoxins should be removed from the list of select
agents and toxins for the following reasons:
Commenters noted that most components isolated from cone
snail venom are harmless to humans; in fact, one of them (MVIIA =
Ziconotide = PrialtTM) is an FDA-approved commercial drug
for the treatment of chronic pain. Several other conopeptides have
reached clinical trials at various levels (CVID, Conantokin-G,
Contulakin-G, Xe2174 and ACV1 = [alpha] conotoxin Vc1.1), and they all
show extremely low levels of toxicity to humans.
Commenters pointed to the fact that the term ``conotoxin''
can be applied to several hundred thousand compounds found in Conus
venoms that are not toxic at all to humans is evidence that this
designation needs to be revised. Furthermore, the designation of
``conotoxins'' as select toxins imposes an enormous and unnecessary
burden for the development of cone snail-based therapeutics.
Other comments included the following:
Conotoxins have never been weaponized.
Conotoxins must be delivered parenterally.
Conotoxins are difficult to manufacture.
Conotoxins are not self[hyphen]replicating.
We agree, in part, with the commenters. Based upon available
experimental evidence, most known conotoxins (i.e., ``conopeptides'')
do not possess sufficient acute toxicity to pose a significant public
health threat, and many are employed as useful research tools or
potential human therapeutics. However, currently available data
demonstrate that the sub-class of conotoxins generally called ``short,
paralytic alpha conotoxins,'' exemplified by [alpha]-conotoxin GI and
[alpha]-conotoxin MI do possess sufficient acute toxicity by multiple
routes of exposure, biophysical stability, ease of synthesis, and
availability. Therefore, we have modified the type of conotoxins that
are regulated to focus on those that pose a threat to public health and
safety. The conotoxins that remain on the HHS list will be limited to
the short, paralytic alpha conotoxins containing the following amino
acid sequence
X1CCX2PACGX3X4X5X
6CX7, whereas:
(a) C = Cysteine residues (indicated in bold) are all present as
disulfides, with the 1st and 3rd Cysteine, and the 2nd and 4th
Cysteine forming specific disulfide bridges;
(b) The consensus sequence includes known toxins [alpha]-MI and
[alpha]-GI (shown above) as well as [alpha]-GIA, Ac1.1a, [alpha]-
CnIA, [alpha]-CnIB
(c) X1 = any amino acid(s) or Des-X;
(d) X2 = Asparagine or Histidine;
(e) P = Proline;
(f) A = Alanine;
(g) G = Glycine;
(h) X3 = Arginine or Lysine;
(i) X4 = Asparagine, Histidine, Lysine, Arginine,
Tyrosine, Phenylalanine or Tryptophan;
(j) X5 = Tyrosine, Phenylalanine, or Tryptophan;
(k) X6 = Serine, Threonine, Glutamate, Aspartate,
Glutamine, or Asparagine;
(l) X7 = Any amino acid(s) or Des X; and
(m) ``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.
The short, paralytic alpha conotoxins containing the following
amino acid sequence
X1CCX2PACGX3X4X5X
6CX7 will be considered a select toxin if the
total amount (all forms) under the control of a principal investigator,
treating physician or veterinarian, or commercial manufacturer or
distributor exceeds 100 mg at any time (Ref 9-13). As such, we have
added the definition of regulated conotoxins.
Removal of Coccidioides Posadasii/Coccidioides Immitis
We are removing C. posadasii/C. immitis from the HHS list of select
agents and toxins. We proposed the removal of C. posadasii/C. immitis
based on the availability of licensed treatments for Coccidioides
infection and a lowering of our assessment of the impact of
Coccidioides infection on human health, as indicated by the high
proportion of subclinical cases observed in endemic areas (Ref 14). The
only comments that we received on this issue were supportive of the
removal of C. posadasii/C. immitis from the HHS list of select agents
and toxins.
Removal of Flexal Virus
We are removing Flexal virus from the HHS list of select agents and
toxins. We proposed the removal of Flexal virus based on the lack of
severity of disease and the lack of significant outbreaks of disease
associated with this virus in humans. The only comments that we
received on this issue were supportive of the removal of Flexal virus
from the HHS list of select agents and toxins.
Removal of the West African Clade of Monkeypox Virus
We are excluding the West African clade of Monkeypox from
regulation under this part, while retaining the Congo Basin clade of
Monkeypox. We proposed the retention of Monkeypox on the list of select
agents and toxins, but invited comments on removing the West African
clade of Monkeypox virus from the list. Monkeypox is closely related to
smallpox virus and produces a clinical syndrome similar to that seen
with smallpox. Mortality rates associated with Monkeypox infections
have been reported to be as high as 17 percent (Ref 15-16). Monkeypox
can be separated into two genetically distinct variants called the West
African and Congo Basin clades. Clinical and laboratory studies
indicate that the Congo Basin clade is significantly more pathogenic to
humans and animals than the West African clade (Ref 17-18). The 37
confirmed cases of human Monkeypox associated with the 2003 importation
of a West African strain from Ghana into the United States were
associated with no case-fatalities and no observed chain of human-to-
human transmission. Clinically severe human disease associated with
West African strains is rare and this virus clade has not been
associated with human mortality (Ref 19). Based on this information, we
are excluding the West African clade from regulation under this part,
while retaining the Congo Basin clade.
One commenter disagreed with the proposed retention of Monkeypox
virus, regardless of clade, as a select agent. We agreed in part with
the commenter. As indicated above, we recognize that significant
differences in pathogenicity exist between the West African and Congo
Basin clades and have determined that viruses of only the Congo Basin
clade merit regulation as HHS select agents. We also note that there
are published diagnostic tests that differentiate Congo Basin from West
African clades (Ref 19).
While the listing found in section 3 (HHS select agents and toxins)
will continue to read ``Monkeypox'', a new subparagraph (d)(5) in that
same section, excludes from regulation any West African clade of the
Monkeypox virus provided that an individual or entity can verify that
the Monkeypox virus is the West African clade.
Removal of South American Genotypes of Eastern Equine Encephalitis
Virus (EEEV)
We proposed the removal of South America EEEV genotypes from the
list of HHS select agents and toxins and the final rule is consistent
with the proposed rule.
One commenter believed that all strains of EEEV should be removed
from
[[Page 61089]]
the select agent list for the following reasons:
The commenter noted that EEEV is endemic in Florida, but
does not cause human epidemics even with high prevalence in the
ecosystem and evidence of natural transmission activity to sentinels.
The commenter noted that person-to-person transmission
does not occur; transmission is only through mosquito bite. An average
of only 5 human cases are identified annually in the United States.
The commenter noted that there is a vaccine available for
horses that can prevent disease even if there is ongoing natural virus
transmission.
The commenter noted that states with high endemicity of
EEEV often have a state public health laboratory proactive
comprehensive arbovirus surveillance program to define risk of human
infection. Serum-neutralization assays are an essential part of such a
program and require live virus which is needed for test performance.
This work is performed at BSL3 level and additional federal regulatory
requirements do not add to the safety of handling or storing the virus.
The commenter noted that genotype analysis to determine if
an EEEV strain is a North American or South American genotype is not
practical in a state public health laboratory, where the goal is
surveillance, not research.
The commenter noted that this agent is not stable in the
environment outside of its natural host (mosquitoes, birds).
We made no changes to the list of HHS select agents and toxins
based on this comment. North American EEEV (NA EEEV), genotype strains,
which are the strains responsible for human and equine disease, are all
genetically very similar to each other (less than 3 percent divergence
at the nucleotide level) and can be easily distinguished from South
American EEEV (SA EEEV) genotype strains by sequencing. NA EEEV
genotype strains differ from SA EEEV by greater than 20 percent at the
nucleotide level and approximately 10 percent at the amino acid level.
We are aware that EEEV is endemic in Florida, that person-to-person
transmission does not occur, that an equine vaccine is available, and
that EEEV isn't stable outside of its natural host. Among the factors
that we considered in retaining the NA EEEV genotype were that this
genotype exhibits high morbidity, high mortality, and has the potential
to be weaponized. We also appreciate that public health laboratories
focus on surveillance and utilize assays that do not specifically
determine which subtype of EEEV is present. However, we believe that
the risks posed by the NA EEEV outweigh the practical issues associated
with subtype determination. Because the NA EEEV genotype strains are
distinctly different from SA EEEV in their genetics, epidemiology, and
pathogenicity, we believe that the two genotypes can be distinguished
from each other in the laboratory.
While the listing found in section 3 (HHS select agents and toxins)
will continue to read ``Eastern Equine Encephalitis virus,'' a new
subparagraph (d) (5) in that same section excludes from regulation, any
South American genotypes of Eastern Equine Encephalitis virus provided
that an individual or entity can verify that the Eastern Equine
Encephalitis virus is one of the South American genotypes.
Rickettsia prowazekii and Rickettsia rickettsii
The proposed rule retained R. rickettsii and R. prowazekii on the
HHS list of select agents and toxins. The final rule removes R.
rickettsii and retains R. prowazekii.
Commenters argued that R. rickettsii and R. prowazekii should be
removed from the select agent list based on:
The same rationale used by HHS/CDC to propose removal of
Herpes B virus from the HHS select agent list;
R. rickettsii and R. prowazekii are readily available in
nature, and can be isolated from natural sources such as ticks and
flying squirrel lice;
R. rickettsii and R. prowazekii are not contagious;
Human infections due to these agents are capable of being
treated with doxycycline, other tetracyclines, and chloramphenicol;
The bacteria are fastidious obligate intracellular
pathogens, thus propagation requires growth in cultured host cells; and
The inclusion of these rickettsiae on the HHS select agent
list will produce no significant improvements in safety for the
American public.
After careful consideration of these comments, we agree with the
commenters that R. rickettsii should be removed from the HHS list of
select agents and toxins. Significant factors in our reconsideration
include the poor environmental stability of this species, the lack of
person-to-person transmission especially in the absence of an
appropriate vector, the availability of effective antibiotic
treatments, and the difficulty in growing and purifying substantial
quantities of these agents in vitro. However, we have determined that
R. prowazekii should be retained as a select agent. This species was
investigated as a potential weapon by multiple national offensive
programs prior to the Biological Weapons Convention, and has many
characteristics of a bioweapon. The infectious dose for R. prowazekii
is unknown but has been estimated to be as little as 10 organisms (Ref
20). There are currently no licensed vaccines against R. prowazekii
available for human use in the United States. Until additional studies
can be completed to better understand the potential risk of an
intentional release of this organism to the public, we have determined
to retain R. prowazekii on the HHS Select Agent List.
Removal of Shigatoxins and Shiga-Like Ribosome Inactivating Proteins
We proposed the retention of Shigatoxins and Shiga-like ribosome
inactivating proteins on the HHS list of select agents and toxins. One
commenter asked us to reconsider the retention of Shigatoxins and
Shiga-like ribosome inactivating proteins as a select toxin based on
the following criteria:
Introduction of Shigatoxins by the aerosol route has not
been reported;
Shigatoxins are extremely difficult to synthesize in
quantities that are toxic to humans;
Expression of toxin in bacteria is self-limiting due to
inhibitory effects on bacterial cells of over-expressed toxin; and
There are limitations to purification and concentration of
Shigatoxins that make them impractical and ill-suited to methods of
dispersal that would require large quantities of toxin for delivery by
food, water, or air.
We have considered all of the points raised by the commenter and,
after additional consultations with subject matter experts, agree that
compelling data exist to support the removal of Shigatoxin and Shiga-
like ribosome inactivating proteins from the HHS list of select agents
and toxins. Therefore, we have decided to remove Shigatoxin and Shiga-
like ribosome inactivating proteins from the HHS list of select agents
and toxins. Additional significant factors considered in our
determination include the difficulty in producing or administering
large quantities of toxin via the aerosol route, their poor
environmental stability, the lack of significant toxicity seen with
oral exposure (which is the route by which an individual becomes
intoxicated by Shigatoxin), and the observation that the worst effects
seen with intoxication are associated with other pathogenic factors
from the Shigatoxin-producing strains of E. coli, which are not
regulated.
[[Page 61090]]
Reduction of Staphylococcal Enterotoxins on the HHS List of Select
Agents and Toxins
We proposed the reduction of Staphylococcal Enterotoxins on the HHS
list of select agents and toxins to only include Staphylococcal
Enterotoxins A, B, C, D, and E. Commenters were concerned that the
``incredible simplicity'' of obtaining Staphylococcal species from
environmental sources and screening them for the presence of
enterotoxins ``utterly neuters'' the intent of the select agent
regulations to provide security against the misuse of such agents. A
commenter requested ``CDC to consider alternative regulatory strategies
to balance the need of legitimate scientific access to such agents so
that it is not harder to use them than for a terrorist.''
We made no changes to the HHS list of select agents and toxins
based on this comment. Current data based on emesis in non-human
primates demonstrates that Staphylococcal Enterotoxins A, B, C, D, and
E pose a significant threat to public health and safety. In addition,
we note that these enterotoxins exhibit significant environmental
stability, which contributes to their public health risk. It should be
noted that this revision represents a significant reduction of the
types of Staphylococcal enterotoxins regulated as HHS select toxins.
Reorganization of Tick-Borne Encephalitis Complex Viruses (TBEV)
We proposed the removal of TBEV Central European subtype from the
HHS list of select agents and toxins because the TBEV Central European
Tick-borne subtype has been shown to be less virulent in humans than
the Far Eastern subtype (Ref 21). We also proposed to reorganize the
listing of the TBEV to reflect the current nomenclature given by the
International Committee on Taxonomy of Viruses. For TBEV proper, there
are now just three recognized subtypes: Central European, Far Eastern,
and Siberian. The Russian Spring and Summer Encephalitis designation is
no longer recognized (Ref 22). Two other viruses on the HHS list of
select agents and toxins, Kyasanur Forest Disease virus and Omsk
Hemorrhagic Fever virus, are no longer classified as TBEV. In
recognition of these taxonomic changes, we proposed to include these
viruses on the HHS list of select agents and toxins as follows:
Tick-borne encephalitis virus
Far Eastern subtype
Siberian subtype
Kyasanur Forest disease virus
Omsk Hemorrhagic fever virus.
All comments that we received on this issue were supportive of the
removal of TBEV Central European subtype from the HHS list of select
agents and toxins and the reorganization of the listing of the TBEV to
reflect the current nomenclature.
Retention of Coxiella burnetii
We proposed the retention of C. burnetii on the HHS list of select
agents and toxins. Commenters argued that this agent should be removed
because:
This organism is ubiquitous in the United States, and can
be detected in greater than 90 percent of bulk milk tank samples.
Despite this, significant human consequences to infection with this
agent are rare.
The organism is readily susceptible to available
antibiotics.
While perhaps easily transmitted to humans, the disease caused by
this organism is generally mild and self-limiting in humans and does
not have a huge economic impact in animals. It therefore does not have
the potential to be an effective terrorist weapon. We made no changes
to the HHS list of select agents and toxins based on these comments. We
recognize that there is a low level of mortality associated with this
agent; that it is present in some bulk unpasteurized milk supplies; and
that antibiotics are available to treat this disease. However,
treatment of chronic Q fever caused by C. burnetii requires antibiotic
regimens that can last for periods up to several years. This long-term
treatment is associated with significant adverse effects and relapse is
common upon withdrawal of the treatment (Ref 23). The determination to
retain C. burnetii on the HHS list of select agents and toxins is based
on multiple factors, including its environmental stability, ease of
transmission to humans, extremely low infectious dose, high morbidity,
its ability to incapacitate large numbers of people, and its prior
history of weaponization. Historical records indicate that extensive
development occurred in the use of this agent as an incapacitating
weapon.
Retention of Diacetoxyscirpenol, Saxitoxin, T-2, and Tetrodotoxin
Toxins
We proposed the retention of Diacetoxyscirpenol, Saxitoxin, T-2
toxin, and Tetrodotoxin on the HHS list of select agents and toxins.
One commenter recommended the removal of these toxins along with Shiga-
like ribosome inactivating proteins, Shigatoxin, Conotoxins, and C.
perfringens epsilon toxin. This commenter stated that ``continuing to
include these toxins on the select agent list has unintended
consequences such as the U.S. Department of Transportation (USDOT)
policies regarding shipment of infectious substances that extends the
list to agents, such as E. coli that produce these toxins, which
results in limiting shipments to public health laboratories.''
Although Shigatoxin producing strains of Escherichia coli are not
subject to the select agent regulations, the removal of Shigatoxin and
Shiga-like ribosome inactivating proteins should positively address the
commenter's concern regarding the USDOT policies. We do not agree with
the commenter that Saxitoxin, T-2 toxin, Tetrodotoxin, and
Diacetoxyscirpenol should be removed from the list. Significant factors
considered in our determination to retain these toxins are their acute
human toxicity, the lack of medical countermeasures or specific
antidotes, and the stability of the toxins in a variety of different
matrices including foodstuffs.
With respect to the comment expressing concerns about the
regulation of E. coli strains that produce these toxins, it should be
noted that nucleic acids that encode for the functional form(s) of
select toxins, if the nucleic acids can be expressed in vivo or in
vitro or are in a vector or recombinant host genome and can be
expressed in vivo or in vitro, are subject to the regulations (See
Sec. 73.3(c)(2)). We consider it important to regulate E. coli strains
that have been modified to produce these materials since they are
capable of producing significant quantities of select toxins. It should
also be noted that E. coli strains that do not contain nucleic acids
that encode for the functional form(s) of select toxins are not subject
to these regulations.
Retention of Yersinia pestis
We proposed to retain Y. pestis on the HHS select agents and toxins
list based on our scientific conclusion regarding the bacterium's high
mortality rate, ease of dissemination and production, and person-to-
person transmission of Y. pestis infections. We received no comments
regarding this proposal.
Overlap Select Agents and Toxins
Reorganization of Venezuelan Equine Encephalitis Virus (VEE)
We proposed the removal of VEE subtypes ID and IE from the list of
overlap select agents and toxins, with subtypes IAB and IC being
retained on the list. Commenters recommended
[[Page 61091]]
removing the entire VEE group from the overlap select agent list
because they believe that current subtyping assays for the
identification of VEE are not sensitive enough to distinguish between
these subtypes. One commenter stated that the subtype IC group can
arise via a single mutation in the ID group and considering VEE's high
mutation rates, an IC subtype can emerge from a laboratory using
subtype ID strains. Commenters also noted that there are two vaccines
available for humans. In addition, commenters argued that the mortality
rate associated with VEE infections via the aerosol route may be very
low.
We made no changes to the overlap list of select agents and toxins
based on these comments. Straightforward diagnostic molecular
techniques, such as sequencing with subtype/variety specific polymerase
chain reaction (PCR) primer sets or serological testing with specific
monoclonal antibodies, can distinguish between enzootic and epizootic
VEE. We also note that based on available data, the emergence of
epidemic subtype 1C from subtype 1D is a rare event. In addition, while
an equine vaccine is available for VEE, human vaccines are limited in
supply and availability.
While the listing found in section 4 (Overlap select agents and
toxins) will read ``Venezuelan equine encephalitis virus,'' a new
subparagraph (d)(3) in that same section excludes from regulation, any
ID and IE serotypes of Venezuelan equine encephalitis virus provided
that an individual or entity can verify that the Venezuelan equine
encephalitis virus is either the ID or IE serotype.
Retention of Bacillus anthracis (Pasteur Strain)
We proposed to designate B. anthracis as a Tier 1 select agent. A
number of commenters objected to such a blanket designation, arguing
instead that the B. anthracis Pasteur strain should be exempted from
consideration either as a Tier 1 select agent or as a select agent in
general.
Commenters argued that because Laboratory Response Network (LRN)
laboratories maintain live cultures of non-pathogenic B. anthracis
Pasteur strain for use in quality control testing, designation of B.
anthracis as a Tier 1 select agent would have the potential to impact
the willingness or ability of LRN laboratories to maintain inventories
of B. anthracis Pasteur strain due to the perceived regulatory and
financial burdens associated with the possession of Tier 1 select
agents and toxins. The commenters went on to state that this situation
could potentially impact national health and safety given that the
potential use of B. anthracis spores as a bioweapon remains a viable
threat. They also argued that the increased regulatory burdens,
particularly on front-line diagnostic laboratories, could lead to an
overall decrease in the number of laboratories that would otherwise
serve to ensure the LRN has sufficient capacity to detect and respond
to a deliberate release of B. anthracis.
Commenters stated that the B. anthracis Pasteur strain is analogous
to the B. anthracis Sterne strain, which has already been excluded
pursuant to section 4(e) of the select agent regulations because it was
determined not to pose a severe threat to public health and safety,
animal health, or animal products. The commenters argued that B.
anthracis Pasteur strain should not be considered as a select agent
given that the only way to create an agent that poses a severe threat
would be to combine the Pasteur strain with a non-regulated strain. The
commenters pointed out that other agents that pose little harm
individually, but could be modified genetically to become harmful, are
not included on the select agent list because of this potential threat.
Another commenter claimed that the designation of B. anthracis
Pasteur strain as a select agent would not serve to prevent an
authorized person from intentionally or accidentally facilitating the
combination of plasmids from Sterne and Pasteur types of strains to
create a wild type phenotype. The commenter stated that combining these
two strains can be accomplished no matter what sort of physical
security may be employed to prevent access, theft, loss, or release of
the agent. The commenter concluded that more effective preventive
measures can be achieved through training and educating microbiologists
on how to avoid accidentally combining these two strains and by
penalizing any individuals who intentionally try to combine them.
We only agree in part with the commenters that it does not meet the
Tier 1 designation, but do not agree to removing it from the select
agent list altogether.
While we agree that the Pasteur strain does not meet the criteria
for inclusion as a Tier 1 select agent, we believe that retaining the
Pasteur strain as a select agent will allow for continued oversight of
laboratories in which the accidental (or intentional) combination of
this strain with the Sterne strain could occur to produce the wild type
phenotype B. anthracis de novo. Failure to retain the Pasteur strain as
a select agent could result in an environment in which the probability
of creating virulent wild type B. anthracis strains by the combination
of non-regulated strains would be enhanced. Therefore, we have chosen
not to exclude the Pasteur strain from the overlap list of select
agents in this rulemaking. We will continue to evaluate exclusion
requests as additional information becomes available in this area.
Retention of Brucella abortus, Brucella melitensis, and Brucella suis
We proposed to retain B. abortus, B. melitensis, and B. suis on the
overlap list of select agents and toxins based on the bacteria's ease
of production, high infectivity via the aerosol route, low infectious
dose, and lack of brucellosis vaccines currently available for humans
in the United States. We received no comments based on this proposal
and will be retaining B. abortus, B. melitensis, and B. suis on the
overlap list of select agents and toxins.
Retention of Burkholderia mallei
We proposed to retain B. mallei on the overlap list of select
agents and toxins based on our determination that the bacteria can be
easily produced in large quantity and transmitted via the aerosol
route. In addition, the mortality rate for untreated cases of glanders
is high, and given the rarity of this disease in the United States,
experience in the diagnosis and treatment is limited. We received no
comments based on this proposal and will be retaining B. mallei on the
overlap list of select agents and toxins.
Retention of Burkholderia pseudomallei
We proposed the designation of B. pseudomallei as a Tier 1 select
agent. Commenters stated that B. pseudomallei should not be a select
agent based on the following criteria:
The criteria by which Coccidioides were proposed by HHS/
CDC to be removed from the list;
B. pseudomallei is non-communicable from person-to-person;
B. pseudomallei lacks a history of use or development as a
successful biologic weapon (as compared with B. mallei, a highly
pathogenic organism with which B. pseudomallei is inappropriately
linked in the list);
B. pseudomallei has a low incidence of symptomatic disease
following natural infection; and
The outcome of 99.9 percent of infections with B.
pseudomallei is asymptomatic infection. Life-threatening illness occurs
only in a few
[[Page 61092]]
hosts with particular risk factors, particularly renal failure and
diabetes.
We disagree with the commenters that B. pseudomallei should be
removed from the overlap list of select agents and toxins. Significant
factors in our determination include the fact that B. pseudomallei is
as virulent in animal models as B. mallei, B. pseudomallei is not
endemic in the United States, B. pseudomallei has a low infectious
dose, B. pseudomallei possesses robust environmental stability, and
timely diagnosis may be complicated because of the rareness of disease
in the United States. In addressing the comment referring to the
criteria used to remove Coccidioides, we note the availability of
licensed treatments for Coccidioides infection and a lowering of our
assessment of the impact of Coccidioides infection on human health as
indicated by the high proportion of subclinical cases observed in
endemic areas. We do not believe that these factors apply to B.
pseudomallei. In addition, we note that B. pseudomallei is not
extensively endemic in the United States as are Coccidioides species.
Therefore, we are retaining B. pseudomallei on the overlap list of
select agents and toxins.
B. Tiering of Select Agents and Toxins
On July 2, 2010, President Obama signed Executive Order 13546
``Optimizing the Security of Biological Select Agents and Toxins in the
United States'' that directed the HHS Secretary to designate a subset
of the select agents and toxins list (Tier 1) that presents 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. In the development of the Tier 1
subset, care was used to balance risks identified in Executive Order
13546 with the Congressional mandate found in the Public Health
Security and Bioterrorism Preparedness and Response Act of 2002 (42
U.S.C. 262a) to ensure the availability of select agents and toxins for
research, education, and other legitimate purposes. Executive Order
13546 also established the FESAP to advise the HHS Secretary on the
designation of Tier 1 agents and toxins, reduction in the number of
agents on the select agent list, establishment of suitability standards
for those having access to Tier 1 select agents and toxins, and the
establishment of physical security and information security standards
for Tier 1 select agents and toxins. Tiering of the select agents and
toxins list will allow for the application of optimized security
measures for those select agents or toxins which pose a higher risk to
public health and safety. A two-part risk analysis was conducted by the
FESAP on each select agent and toxin on the list. First, experts in the
biology of these agents and toxins evaluated their ``potential for mass
casualties or devastating effects to the economy, critical
infrastructure, or public confidence.'' This included assessments of
morbidity and mortality, communicability, infectious dose, availability
of countermeasures, and estimated economic impact of a potential
attack. Second, each agent and toxin was assessed by experts from the
DOD, DHS, and Department of Justice (DOJ) for its ``risk of deliberate
misuse,'' including its history of weaponization and/or known interest
by state or non-state adversaries. In addition, the Federal Select
Agent Program also used information obtained from DHS Material Threat
Determinations in making final decisions regarding their
recommendations as to which select agent or toxin should be designated
as Tier 1. These evaluations in combination with (1) input from public
comments received in response to the NPRM, and (2) relevant findings in
recent government and non-government reports, informed the
deliberations on which agents should be designated as Tier 1, as well
as those that should be removed from the select agent and toxin list.
Agents that scored highly on both the public health and biothreat sets
of criteria were judged to be those that met the criteria for Tier 1.
We have determined that the following agents should be designated as
Tier 1 agents: B. anthracis, Botulinum neurotoxins, Botulinum
neurotoxin producing species of Clostridium, B. mallei, B.
pseudomallei, Ebola virus, F. tularensis, Marburg virus, Variola major
virus, Variola minor virus, and Y. pestis.
Commenters questioned why we believe that the current regulations
were not sufficient to contain, secure, and protect the proposed Tier 1
select agents and toxins from theft, loss, exposure, or release. In
response, we note that the absence of clearly defined, risk-based
security measures in the select agent regulations raised concern both
by stakeholders within the Executive Branch and outside the government.
This is the focus of Executive Order 13486 (Strengthening Laboratory
Biosecurity in the United States) and Executive Order 13546 (Optimizing
the Security of Biological Select Agents and Toxins in the United
States) that call for improvements in select agent security and risk
management. The additional security requirements for those entities
possessing Tier 1 select agents and toxins will enhance physical
security, personnel suitability, and information security within the
affected entities.
The commenters further contended that the proposed regulatory
changes failed to achieve the goal of minimizing the impact of the
regulations on the legitimate uses of select agents and toxins that
Executive Order 13546 notes are essential to national security. In
response, we note that the overall number of select agents and toxins
has been reduced, lessening the overall regulatory burden. In addition,
by maintaining a performance-based approach in the regulations, we are
allowing regulated entities to develop policies and procedures that
meet the new requirements of the regulations while accommodating
specific operational aspects of each entity.
Other commenters stated that the proposed tiering system poses
significant questions as to the nature of the risk assessment process.
Specifically, commenters questioned listing as Tier 1 agents bacterial
diseases that are treated with licensed antibiotics, that are not
commonly spread person-to-person, and that are present in the
environment of the United States; while viruses that have no known
therapy and that pose extreme risk to western populations are absent
from the Tier 1 list. The commenters believed that the 20 criteria used
for evaluation of each select agent and toxin should be made available
to the regulated community for review and assessment. We note that the
20 criteria referenced by the commenters were the ones used by the
FESAP in providing recommendations to the Federal Select Agent Program.
Nevertheless, we agree with the commenters that it is reasonable to
publish the criteria used by the FESAP in providing the tiering
recommendations to the Federal Select Agent Program. These criteria
are:
1. The relative ease with which a select agent or toxin might be
acquired from a laboratory or commercial source;
2. The relative ease of production of a select agent or toxin;
3. The relative ease by which a select agent or toxin might be
modified in order to enhance its pathogenicity, transmissibility, or
ability to evade medical and non-medical countermeasures;
4. The potential for easy deliberate dissemination;
5. The potential for creating disease or illness;
6. The relative environmental stability of a select agent or toxin
by itself and how well it survives in the environment
[[Page 61093]]
in which it is formulated or disseminated;
7. The amount of select agent or toxin necessary to induce illness;
8. The relative ease with which a particular select agent or toxin
might be disseminated or transmitted from one animal or person to
another or into the environment where it could produce a deleterious
effect upon animal, plant, or human health;
9. Whether the target population has innate immunity to the select
agent or toxin or whether immunity has been acquired from a source such
as vaccines;
10. The potential for the select agent or toxin to create morbidity
(i.e., any non-fatal illness that renders partial dysfunction to an
animal or human lasting weeks or months that will eventually resolve
with medical, veterinary, and/or supportive care);
11. The burden placed on the human, veterinary, or plant health
system by the deliberate release of the select agent or toxin;
12. The ability to detect a release of the select agent or toxin
into the environment, food, water, or soil;
13. The ability of the human and agricultural health authorities to
accurately and rapidly diagnose and treat the disease presented by a
release of the select agent or toxin;
14. The existence of countermeasures to prevent, treat, or mitigate
the symptoms of a disease caused by the release of a select agent or
toxin and/or its spread through a population;
15. The potential for high animal, plant, or human mortality rates
with delivery of medical countermeasures;
16. The potential for high animal, plant, or human mortality rates
without delivery of medical countermeasures;
17. The short-term economic impact of a single outbreak of a
disease or release of a toxin;
18. The human, monetary, and other resource costs of making an
area, building, industrial plant, farm, or field safe for humans,
animals or plants to inhabit following the release of the select agent
or toxin;
19. The pathogen's ability to persist in the environment or to find
a reservoir that makes its recurrence more likely; and
20. The long-term health or economic consequences caused by a
single release of the select agent or toxin.
Commenters argued that if there is a ``Tier 1'' designation of
certain select agents and toxins, there logically should be a list of
designated ``Tier 2'' select agents and toxins. We made no changes
based on this comment. In designating certain select agents and toxins
as ``Tier 1,'' the Federal Select Agent Program considered and rejected
the idea of designating the remaining agents as ``Tier 2'' because the
establishment of the Tier 1 category is in no way intended to imply
that the agents not designated as Tier 1 pose a lesser risk to public
health and safety than they have previously. Further, we believe that
the establishment of more varying levels of risk categories would
create an increased administrative oversight burden and needless
complications for regulated entities.
Various commenters argued that the following select agents should
be not be listed as Tier 1 agents: F. tularensis, Y. pestis, B. mallei,
B. pseudomallei, and B. anthracis because these bacteria are all
readily found in the environment and treated effectively with
antibiotics, such that additional security requirements will have
little or no effect on biodefense. Commenters said they recognized that
public perception must be taken into account, but they stated a belief
that there is little public recognition of many of these bacteria as
potential biothreat agents. Commenters stated that F. tularensis is not
transmissible from one human to another nor does it have either the
potential for major human health impact or the potential for a high
mortality rate.
Based on the FESAP recommendation using the criteria identified
above, we disagree with the commenters that F. tularensis should not be
designated as a Tier I select agent. Significant factors that we
considered include the low infectious dose, the robust environmental
stability, and a well-documented history of weaponization associated
with this agent.
Commenters stated that B. pseudomallei should be not be listed as
Tier 1 agent because B. pseudomallei is non-communicable from person-
to-person, lacks a history of use or development as a successful
biologic weapon (as compared with B. mallei, a highly pathogenic
organism with which B. pseudomallei is inappropriately linked in the
list), and has a low incidence of symptomatic disease following natural
infection. The outcome of 99.9 percent of infections with B.
pseudomallei is asymptomatic infection. Life-threatening illness occurs
only in a few hosts with particular risk factors, particularly renal
failure and diabetes.
Based on the FESAP recommendation using the criteria identified
above, we disagree with the commenters that B. pseudomallei should not
be designated as a Tier I select agent. Significant factors in our
determination include the fact that B. pseudomallei is as virulent in
animal models as B. mallei, B. pseudomallei is not endemic in the
United States, B. pseudomallei has a low infectious dose, B.
pseudomallei possesses robust environmental stability, and timely
diagnosis may be complicated due to the rareness of disease in the
United States. In addressing the comment referring to the criteria used
to remove Coccidioides, we note the availability of licensed treatments
for Coccidioides infection and a lowering of our assessment of the
impact of Coccidioides infection on human health, as indicated by the
high proportion of subclinical cases observed in endemic areas. We do
not believe that this applies to B. pseudomallei. In addition, we note
that B. pseudomallei is not extensively endemic in the United States as
are Coccidioides species. Therefore, B. pseudomallei will be listed as
a Tier 1 select agent and toxin.
Commenters stated that Botulinum toxin should not be identified as
a Tier 1 agent because Botulinum toxin is a non-replicating, non-
infectious chemical agent and should not be in the same category as
highly contagious biological agents such as B. anthracis or un-
treatable agents such as the Ebola virus. We made no changes based on
these comments. We are aware that Botulinum toxin is a non-replicating
and non-infectious toxin. However, the rule seeks to balance the
regulatory oversight of agents and toxins that have the potential to
pose a severe threat to public health and safety while maintaining
availability of these agents and toxins for research and educational
activities. Another commenter further argued that Botulinum neurotoxin
quantities in excess of 500 microgram ([mu]g) should be designated as
Tier 1 toxin, but quantities of less than 500 [mu]g should not be
regulated. One commenter questioned the ``logic (or science)'' behind
this decision, particularly when pharmaceutical production facilities
possessing greater than 500 [mu]g will be exempt from the new
regulations.
We noted that the pharmaceutical production facilities possessing
select agent or toxins are currently regulated under select agent
regulations. However, products that are, bear, or contain listed select
agents or toxins that are cleared, approved, licensed, or registered
under any of the laws specified in Section 5(c) and 6(c) of the
regulations are exempted from the requirements of the select agent
regulations, insofar as their use is only for the approved purpose and
meets the requirements of such laws. The exemption would only apply to
the final product created from or containing the select agent or toxin.
The amount of each toxin that could be possessed
[[Page 61094]]
without regulation by a principal investigator, a treating physician or
veterinarian, or a commercial manufacture 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. The
level specified in the rule was determined after consultation with
subject matter experts on this toxin. The determination that a toxin
posed a severe public health threat was based on the ability for the
mass distribution of the toxin for mass casualty purposes. Therefore
Botulinum neurotoxin will be placed on the HHS Tier 1 list of select
agents and toxins.
Commenters stated that Ebola and Marburg viruses should be removed
from Tier 1 because none of the other hemorrhagic fever viruses are in
Tier 1, yet they are just as dangerous. We disagree with the commenters
and note that the hemorrhagic viruses on the select agent list exhibit
distinct differences in morbidity, mortality, transmissibility, and
degree of pathogenicity. Therefore our consideration to designate a
particular virus as Tier 1 is made on a virus-by-virus basis. Ebola
virus and Marburg virus are designated as Tier 1 select agents.
Reconstructed Replication Competent Forms of the 1918 Pandemic
Influenza Virus Containing Any Portion of the Coding Regions of all
Eight Gene Segments (Reconstructed 1918 Influenza Virus)
One commenter argued that Reconstructed 1918 Influenza virus should
be a Tier 1 select agent since it is a pathogenic agent not currently
present in any human population and not currently present in any
natural environment. The commenter further argued this agent exhibited
high transmissibility and high lethality and caused a global pandemic
with massive mortality (>=50 million deaths; >=3 percent of the human
population at the time), massive economic impact, and major
psychological impact when last present in human populations.
We did not propose to designate Reconstructed 1918 Influenza virus
as a Tier 1 select agent and are making no changes to the HHS list of
select agents and toxins based on this comment. Recent studies have
increased our understanding of the public health risks associated with
this agent. Current reports suggest that as much as 60 percent of the
population in the United States may have some immunity to the 1918
Influenza virus. We also considered the potential availability of
vaccines and antiviral treatments when considering whether to designate
this virus as a Tier 1 select agent.
Although we did not designate the Reconstructed 1918 Influenza
virus as a Tier I select agent, we retained this virus as a select
agent. In retaining this virus as a select agent we recognize that, to
the best of our knowledge, the only place the Reconstructed 1918
Influenza virus currently resides is in laboratories. Unlike other
influenza viruses, the most likely source of a Reconstructed 1918
Influenza virus outbreak would be as a result of a breach or failure of
a laboratory's biosafety or biosecurity program.
Diagnostic Laboratories and Tier 1 Agents
Commenters have expressed concerns about the ability of diagnostic
laboratories, such as those in the LRN, to retain their ability to
perform diagnostics while meeting the requirements for Tier 1 select
agents and toxins. The Federal Select Agent Program recognizes the
critical role of diagnostic laboratories in the early detection and
response to outbreaks of disease in humans and agriculture. While all
of the Tier 1 regulatory requirements will apply to laboratories that
maintain permanent stocks of Tier 1 select agents and toxins,
laboratories may wish to consider maintaining their proficiency in
detecting Tier 1 select agents and toxins through the use of excluded
attenuated strains of select agents and toxins that meet their testing
requirements. Examples of excluded attenuated strains include: B.
anthracis strains devoid of the plasmid pX02 (e.g., B. anthracis
Sterne, pX01+pX02-) (effective 2-27-2003), F. tularensis subspecies
holartica LVS (live vaccine strain; includes NDBR 101 lots, TSI-GSD
lots, and ATCC 29684) (effective 2-27-2003), and Y. pestis strains
(e.g., Tjiwidej S and CDC A1122) devoid of the 75 kb low-calcium
response (Lcr) virulence plasmid (effective 2-27-2003). Possession of
an excluded attenuated strain, so long as it has not been subjected to
any manipulation that restores or enhances its virulence, would be
excluded from the HHS and USDA select agent regulations. Those
laboratories encountering a Tier 1 select agent or toxin in their
routine work with diagnostic or proficiency testing, would still
qualify for the clinical or diagnostic laboratory exemption found in
sections 5(a) and 6(a) of the regulations. Should a diagnostic
laboratory wish to maintain a select agent identified in a diagnostic
sample longer than the seven calendar days currently allowed by the
select agent regulations, the diagnostic laboratory can request that
HHS/CDC or USDA/APHIS grant additional time before the select agent is
transferred or destroyed pursuant to either section 5(a) or section
6(a) of the regulations.
C. Responses to Other Proposed Changes
With respect to the remainder of the sections outlined below, the
following changes are based on comments received in response to the
NPRM and recommendations from the FESAP. We updated the Web address
throughout the document as all information concerning the Federal
Select Agent Program is now centralized on the National Select Agent
Registry (NSAR) at http://www.selectagents.gov/. In addition, HHS/CDC
and USDA/APHIS used similar language in our final rules to ensure
consistency between the regulations.
Definitions
Occupational Exposure
We proposed to add a definition for occupational exposure based on
the definition used in the Occupational Safety and Health
Administration (OSHA) regulations found in 29 CFR 1910.1030 (Bloodborne
pathogens). Commenters proposed that we not use the OSHA definition
since the adoption of this definition would limit possible exposures to
select agents only to bloodborne pathogens and to other potentially
infectious materials as noted in that standard, but not to occupational
exposure to aerosols of the agents in the select agent list. One
commenter recommended ``a definition, which combines the OSHA
bloodborne pathogens standard and the definition of ``exposure
incident'' found in the Bloodborne Pathogen Standard and Exposure
Incident (Laboratory) from the Cal/OSHA Aerosol Transmissible Diseases
(California Code of Regulations, Title 8, Section 5199), to ensure that
both non-aerosol and aerosol exposure events are appropriately
addressed that would state ``Exposure Incident: Any event which results
in (1) an individual experiencing a specific eye, mouth, or other
mucous membrane, non-intact skin, or parenteral contact with a select
agent or toxin; or (2) an individual experiencing a potential exposure
to an aerosolized select agent without the benefit of appropriate
exposure controls, and the circumstances of the aerosol exposure make
the transmission of a disease sufficiently likely that the individual
requires further medical evaluation by a
[[Page 61095]]
Physician or other licensed health care professional.'' We agree with
the commenters and are revising the definition to state: ``Any
reasonably anticipated skin, eye, mucous membrane, parenteral contact,
or respiratory aerosol exposure to select agents or toxins that may
result from the performance of an employee's duties.''
Recombinant and Synthetic Nucleic Acids
We proposed to add the definitions for recombinant and synthetic
nucleic acids to the regulations. One commenter stated that the broad
definition has implications in all areas of synthetic biology
technology, including industrial enzymes, renewable chemicals for
pharmaceutical and industrial applications, biobased products, personal
care products, renewable specialty chemicals, biofuels, and healthcare
products. The commenter argued that the consequences of such a
definition could impede the growth of sustainable products from an
emerging science such as synthetic biology technology. The commenter
recommended that we not adopt the new definitions of recombinant and
synthetic nucleic acids as put forth in the proposed rule because the
existing language of the regulation is sufficient to cover the uses of
synthetic nucleic acids as currently practiced; and furthermore, that
the proposed definitions utilize language that was proposed to, but
rejected by, the NIH Recombinant DNA Advisory Committee (NIH-RAC). The
commenter further argued that if we feel compelled to introduce a new
definition, that we follow the leadership of the NIH-RAC and promulgate
a simpler definition that is not focused on the underlying mechanism of
production of the nucleic acids. We made no changes to the definition
based on this comment. The scope of our oversight is limited by the
list of select agents and toxins and therefore does not extend to all
synthetic biology. We have updated the organization of the definitions
of recombinant and synthetic nucleic acids upon consultation with the
NIH Office of Biotechnology Activities. The definitions now read as:
Recombinant nucleic acids. (a) Molecules that are
constructed by joining nucleic acid molecules and that can replicate in
a living cell (i.e., recombinant nucleic acids) or (b) molecules that
result from the replication of those described in (a) above.
Synthetic nucleic acids. (a) Molecules that are chemically
or by other means synthesized or amplified, including those that are
chemically or otherwise modified but can base pair with naturally
occurring nucleic acid molecules (i.e., synthetic nucleic acids) or (b)
or molecules that result from the replication of those described in (a)
above.
In addition, we have separated the definition of recombinant and
synthetic nucleic acids for clarity.
Restricted Person
We proposed to add the definitions for the following terms in 42
CFR 73.1, to clarify the criteria related to the identification of a
restricted person: Adjudicated as a mental defective, Alien, Committed
to any mental institution, Controlled substance, Crime punishable by
imprisonment for a term exceeding 1 year, Indictment, Lawfully admitted
for permanent residence, Mental institution, Restricted person, and
Unlawful user of any controlled substance. Commenters stated that
proposed definitions need to be further clarified and are overly
restrictive or vague. We agree with these comments and are not
including these definitions in this final rule.
Exclusions
We proposed to remove language stating that an attenuated strain of
a select agent that had been granted an exclusion because it did not
pose a severe threat to public health and safety would be published in
the Federal Register. We received no comments regarding this proposal.
However, one commenter requested clarification regarding previously
established exclusions as currently listed on the NSAR at http://www.selectagent.gov/Select%20Agents%20and%20Toxins%20Exclusions.html.
The commenter stated that individuals should not have to reapply and
secure written approval for those attenuated strains that were
previously recognized as excluded from select agent status.
In response to this commenter, we note that the language posted on
the Federal Select Agent Program Web site at http://www.selectagent.gov/Select%20Agents%20and%20Toxins%20Exclusions.html
already clarifies that once an attenuated strain of a select agent (or
an inactivated select toxin) is determined not subject to the
requirements of select agent regulations, the strain or toxin will only
be subject to regulation if there is any modification such that
virulence is restored or enhanced. Therefore, individuals are not
required to reapply and seek written approval for attenuated strains or
inactive toxins that have already been determined by the Federal Select
Agent Program to be excluded.
As noted earlier, we proposed the removal of the South America
genotypes of EEEV and the VEEV subtypes ID and IE. We have also
excluded the West African clade of Monkeypox virus. To prevent
confusion on how an entity should handle samples that have been
determined to be within a general taxonomic classification (e.g., EEEV)
but not within a particular genotype or subtype (e.g., NA-EEEV), we
have maintained the current general taxonomic listing of HHS and
overlap select agents as opposed to listing a specific strain and added
an exemption for the strains, subtypes, or pathogenicity levels which
are not considered to have the potential to pose a severe threat to
public health and safety. With this change, we believe we have
clarified that when an agent is initially identified by taxonomic
classification it is subject to the select agent regulations until
further testing is accomplished to exclude the particular agent by
strain, subtype, or pathogenicity level. We believe it is important
that laboratories should treat these select agents and toxins as though
they must comply with this part until further testing can be conducted
to verify whether the agent is indeed an excluded strain, subtype, or
pathogenicity level. This change should not have any impact on the
exemption for diagnostic laboratories or alter the process of taking in
diagnostic samples and forwarding any potentially identified select
agents for further testing. It also does not change the reporting
criteria for when the agent is confirmed as a select agent. Therefore,
we are maintaining the listing of select agents in 42 CFR 73.3(b) to
read, Monkeypox virus and Eastern Equine Encephalitis virus, and adding
the following criteria to be excluded in 42 CFR 73.3(d)(5): Any South
American genotypes of Eastern Equine Encephalitis virus and any West
African Clade strains of Monkeypox virus. We are also amending the
proposed list of select agents in 42 CFR 73.4(b) to read Venezuelan
equine encephalitis virus, and adding the following criteria to be
excluded in 42 CFR 73.4(d)(3): Any ID and IE subtypes of Venezuelan
equine encephalitis virus.
Toxins
In 42 CFR 73.3(e) and 73.4(e), we proposed to clarify that the
``inactive form of a select toxin'' may be excluded from regulation
since the current term, ``attenuated strain of toxin'' is
scientifically inaccurate. We received comments that were supportive of
this
[[Page 61096]]
proposed change and will finalize the change in this rule.
We proposed to add 42 CFR 73.3(d)(4) which would state, ``An animal
inoculated with or exposed to an HHS select toxin.'' The change allows
animals injected with or exposed to a select toxin not to be considered
a ``select toxin.'' Therefore, the animals would not need to be housed
in a registered space. The change eliminates an unnecessary burden on a
registered entity because recovering the toxin from within an animal
subject is highly difficult and such removal is unlikely to produce a
reasonable yield of recovery. In addition, there is uncertainty as to
whether the toxin would remain active when recovered from the animal.
For these reasons, it is highly unlikely that once introduced into an
animal, sufficient toxin would be able to be recovered to pose a
significant hazard to public health. We received comments that were
supportive of this proposed change.
One commenter recommended that we clarify that the aggregate amount
in Sec. 73.3(d)(3) is per ``principal investigator, treating physician
or veterinarian, or commercial manufacturer or distributor,'' and not
per entity. We made no changes to the regulations based on this comment
because the current regulatory language provides sufficient protections
against the unrecognized accumulation of regulated quantities of select
toxins at a given entity through multiple procurements of less than
threshold amounts by multiple principal investigators within the
entity. The same commenter recommended that we amend the regulatory
language from ``toxin'' to ``purified toxin.'' The commenter argued
that since there are naturally occurring organisms that produce these
toxins, unless they are purified they will pose only a low-level risk
to human health. We made no changes to the regulation based on this
comment since any HHS select agent or toxin that is in its naturally
occurring environment, provided the select agent or toxin has not been
intentionally introduced, cultivated, collected, or otherwise extracted
from its natural source, is already excluded in section 73.3. The same
commenter also recommended that the guidance be clarified to state that
there are some select toxin-producing organisms that are not covered
under this section of the regulations. Although we agree that there are
indeed toxin-producing organisms that are not covered under this
section of the regulations, we made no changes to the regulation based
on this comment. The regulations clearly state which agents are
regulated. Guidance is also available on the select agent Web site
(http://www.selectagent.gov/SyntheticGenomics.html) and defines the
select agents that are regulated.
Due Diligence
We proposed to require that an entity transferring a toxin in
amounts which would otherwise be excluded from the provisions in 42 CFR
part 73 would be excluded only if the transferor: (1) Uses due
diligence and documents that the recipient has a legitimate need (i.e.,
reasonably justified by a prophylactic, protective, bona fide research,
or other peaceful purpose) to handle or use such toxin; and (2) reports
to HHS/CDC if they detect a known or suspected violation of Federal law
or become aware of suspicious activity related to the toxin. The
majority of our commenters from academic institutions argued that the
proposed toxin due diligence provisions did not improve the safety and
security of excluded quantities of these toxins. The commenters
expressed concerns that if the toxin is being transferred to an
individual employed by an entity which clearly has a bona fide research
purpose, the laboratory providing the material should not have an
obligation to report the transfer. Commenters further requested that
the terms, ``due diligence'' and ``legitimate need'' be clarified. We
made no changes to the regulation based on these comments. The proposed
amended regulatory language to require due diligence and the reporting
of known or suspected violations of Federal law in this case addresses
concerns that an individual may be able to accumulate, unnoticed by
anyone, regulated amounts of a select toxin by stockpiling shipments of
unregulated amounts. We believe that commercial manufacturers and
distributors already track the shipments of toxins as part of their
quality management systems. We note that entities registered with the
Federal Select Agent Program are already required to maintain records
of internal toxin transfers. We are not defining either ``due
diligence'' or ``legitimate need'' in the regulatory language because
we believe both of these terms to be widely used and commonly
understood. We would expect that, before transferring any amount of a
select toxin, a reasonable person would satisfy themselves that the
recipient had a legitimate need for a prophylactic, protective, bona
fide research, or other peaceful purpose. We also note that while the
transfer has to be recorded, the only report required by the new
regulatory language is a report of a transfer believed or suspected to
be a violation of law.
Exemptions
Immediate Notification of the Identification of a Select Agent or Toxin
Contained in a Specimen Presented for Diagnosis or Verification
We proposed to amend 42 CFR 73.5 and 73.6 to limit the immediate
notification requirement to only those select agents and toxins
identified as Tier 1 agents and toxins because these agents and toxins
present the greatest risk of deliberate misuse with the most
significant potential for mass casualties. We received comments that
were supportive of this proposed change and we are finalizing this
requirement in this rule.
Public Health Emergency
To eliminate an unnecessary burden on any individual or entity
responding to a domestic or foreign public health emergency, we have
removed the provision that the individual or entity must complete an
APHIS/CDC Form 5 to request an exemption. Guidance on requesting an
exemption for an individual or entity to respond to a domestic or
foreign public health emergency may be found on the select agent Web
site at www.selectagents.gov.
Responsible Official
Alternate Responsible Official
We proposed to add language to clarify the role of an alternate
Responsible Official in order to definitively establish that an
alternate Responsible Official must have the full knowledge and
authority to act for the Responsible Official in his/her absence. While
commenters generally agreed, one commenter argued that the proposed
changes would prohibit consultants from serving as an alternate
Responsible Official. We are making no changes to the regulation in
response to this comment. We first note that in the absence of the
Responsible Official, a person who has been designated by the entity as
an alternate Responsible Official becomes the entity's Responsible
Official. We believe that an individual acting as a consultant would
have neither the institutional authority nor responsibility to allow
them to serve as an alternate Responsible Official. This does not mean
that an entity Responsible Official cannot utilize the services of a
consultant in carrying out his or her duties. But the regulations were
designed to require an entity to vest authority and responsibility for
ensuring compliance with the select
[[Page 61097]]
agent regulations in one entity official so that the person can take
action in the name of the entity and on behalf of the entity, and not
merely provide advice or consultation.
Commenters also recommended that a provision for delegation of
responsibilities to an alternate Responsible Official by the
Responsible Official should be included, even with the Responsible
Official present, so that an alternate Responsible Official would
always be acting under the direction/oversight of the Responsible
Official. Other commenters felt that it would be practical for the
Responsible Official to delegate an alternate Responsible Official who
is housed in the remote facility to take on the day-to-day
responsibilities of the Responsible Official in that facility. We are
making no changes to the regulations in response to these comments
because the regulations already provide to the Responsible Official the
flexibility to delegate the authority to perform certain tasks. While
the regulations allow the Responsible Official as many assistants as
he/she needs to ensure compliance with the regulations, the Responsible
Official retains the ultimate responsibility for compliance. The
regulatory provisions for the appointment of an alternate Responsible
Official are in recognition of the fact that, as a practical matter, a
single person cannot always be present at an entity. We believe that it
is important for each entity to identify the person who has the
responsibility for that entity to ensure compliance with the select
agent regulations and this approach will help achieve a higher level of
compliance than would be obtained from a system of shared
responsibility.
Duty Station
We proposed to add a requirement that the Responsible Official's
regular place of employment or principal duty station must be located
in close proximity to the physical location of the registered entity
entered in section 1A of APHIS/CDC Form 1 (Application for Registration
for Possession, Use, and Transfer of Select Agents and Toxins). As we
stated in the preamble to the proposed rule, we believed that the
Responsible Official should have a physical (and not merely a
telephonic or audio/visual) presence at the entity to ensure that the
entity is in compliance with the select agent regulations and be able
to quickly respond to on-site incidents involving select agents and
toxins. Commenters generally agreed with the requirement that the
Responsible Official's regular place of employment or principal duty
station must be co-located with the physical location of the registered
entity entered in section 1A of APHIS/CDC Form 1. One commenter
recommended that we eliminate the requirement for the definition
because the Responsible Official is frequently a high-level
administrator at a university, such as a Vice President for Research,
and it would be infeasible in many cases for such a Responsible
Official, whose duties extend beyond biosecurity, to be physically
located at a registered entity; it would only add a layer of
bureaucracy, which could detract from a focus on security, to require a
second, on-site Responsible Official. We made no changes based on this
comment. As noted above, the Responsible Official should be an
individual who can perform all of the duties required for that
position. The regulations were designed to place responsibility for
ensuring compliance with the regulations in one position. However, some
commenters requested that we clarify the provision regarding the
individual's principal duty station, physical location, and ``close
proximity with the physical location of the registered entity.'' In
addition, one commenter requested that we explain how quickly the
Responsible Official should be able to respond to onsite incidents in
terms of turnaround time. Another commenter stated that they were not
persuaded that ensuring compliance and a quick response to incidents
are sufficient rationale for this requirement.
In response, we are changing the language in section 73.9 to
clearly state that the Responsible Official 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 is able to quickly respond to on-site incidents
involving select agents and toxins. We recognize that some entities are
located on a campus with several registered laboratories situated in
different buildings throughout the campus, and we believe it would be
counterproductive to require that the Responsible Official be assigned
to each physical laboratory listed on the entity's registration and
require a set turnaround time to respond quickly to on-site incidents.
However, the Responsible Official should be able to respond in a timely
manner to onsite incidents in accordance with the entity's incident
response plan. The regulations also contain a performance standard that
the Responsible Official is physically located on the campus to ensure
day-to-day oversight and compliance with the select agent regulations
and to respond to any incident in a way that limits damage and ensures
that select agents and toxins are secured and safeguarded.
Responsible Official Training Requirement
We proposed to add a specific requirement that all Responsible
Officials possess the appropriate training or expertise to execute
their required duties. We received multiple comments and concerns about
fulfilling the provisions of this proposed requirement. The breadth and
variety of training and expertise available would be difficult to
capture in regulatory language. Therefore, we will continue to assess
the performance of the Responsible Official based on his or her
efficacy in implementing the select agent and toxin regulatory
requirements at the entity. As such, we have accepted these comments
and have not included this provision in the final rule.
Access to Select Agents and Toxins
Timeframe
We proposed to decrease the maximum length of time in which a
Security Risk Assessment (SRA) will be valid from five years to three
years in order to more expeditiously identify individuals who may have
fallen into one of the prohibited or restricted categories. Commenters
argued that our proposal to shorten this time period would increase the
work load for individuals, entities, the Federal Select Agent Program,
and the Federal Bureau of Investigation (FBI), and would only add
bureaucratic expense for all without any source of compensation to the
investigators and institutions who are endeavoring to contribute
countermeasures against biothreats. Another commenter stated that it
would have a significant impact on law enforcement's ability to handle
the increased workload to conduct these investigations. One commenter
was concerned that there would be delays in SRA approval that would
negatively impact workload performance.
We are making no changes to the regulations based on these
comments. On January 9, 2009, the President signed E.O. 13486 entitled
``Strengthening Laboratory Biosecurity in the United States.'' This
Executive Order established a working group co-chaired by
representatives of the DOD and HHS Secretaries. The scope of working
group activities pertained to the policy of the United States that
facilities that possess biological select agents and toxins have
[[Page 61098]]
appropriate security and personnel assurance practices to protect
against theft, misuse, or diversion to unlawful activity of such agents
and toxins. The working group provided final recommendations through
careful consideration of proposals from subgroups and comments received
from select agent entities and the public. The report is available at:
http://orise.orau.gov/emi/scapa/files/biosecurity-report.pdf.
One of the recommendations from the working group to enhance
security was to perform the SRA every three years for all individuals
with access to select agents and toxins instead of the existing policy
of performing the SRA every five years. We concurred with this
recommendation. Based on input from the FBI, we have determined that
conducting SRA approvals every three years is beneficial in increasing
the security of registered entities. As a policy matter, we have been
processing SRAs on a three-year basis since June 1, 2011 and an
increase in administrative burden has not been noted. We also did not
receive any comments from the regulated community that they have
experienced any additional burdens. Accordingly, we do not believe this
regulatory change will result in an increased burden on registered
entities.
Portability
We also proposed to amend the regulations in section 73.10 to add
new provisions by which individuals may have access to select agents
and toxins at entities other than the individual's ``home'' entity. One
commenter suggested that the Responsible Official, rather than the
individual as proposed, make the request to the HHS Secretary or
Administrator to approve access to select agents or toxins at another
registered entity for a specific period of time. Other commenters
requested clarification of the process and suggested that limiting
access to only one entity at the time would be appropriate.
In response to these comments, we are amending section 73.10 to
provide that ``a person with a valid approval from the HHS Secretary or
Administrator to have access to select agents and toxins may request,
through his or her Responsible Official, that the HHS Secretary or
Administrator provide their approved access status to another
registered individual or entity for a specified period of time.''
One commenter wanted clarification that an individual would have
access to select agents at multiple registered entities based on the
proposed language. The revised language would allow individuals the
flexibility to have access to select agents and toxins at entities
other than the individual's ``home'' entity. To address the commenter's
concern that the SRA portability process is unclear, additional
guidance has been developed and is available at http://www.selectagents.gov.
Security
Animals or Plants Accidentally or Intentionally Exposed to or Infected
With a Select Agent
One commenter was unclear regarding whether the security plan
should contain procedures concerning animals or plants accidentally or
intentionally exposed to or infected with a select toxin. We made no
changes to the regulations based on this comment. As we discussed in
the preamble for the NPRM, we are not requiring the security plan to
address procedures concerning animals exposed to toxins because it is
highly unlikely that once introduced into an animal, sufficient toxin
can be recovered to pose a significant hazard to public health and
safety.
Another commenter wanted to know if the provision was for clinical,
veterinary, or environmental laboratories performing diagnostic work to
identify a select agent in humans, food or environmental samples. We
made no changes to the regulation based on this comment. Any select
agent or toxin that is in its naturally occurring environment (e.g.,
sand samples that are naturally infected with B. anthracis or milk
samples that contain C. burnetii) provided the select agent or toxin
has not been intentionally introduced, cultivated, collected, or
otherwise extracted from its natural source is already excluded in
sections 3 and 4 of the select agent regulations.
Commenters requested that we change the statement of ``safeguarding
of animals or plants intentionally or accidentally exposed to or
infected with a select agent'' to read ``intentionally exposed to, or
infected with, select agents.'' The commenters suggested that the
statement would be clearer. We made no changes to the regulations based
on this comment. We believe that animals or plants accidently exposed
to or infected with a select agent should be handled as a select agent
and safeguarded in the same manner as an animal or plant intentionally
exposed to a select agent.
Codification of Current Practices for Shipping, Receiving and Storage
We proposed to codify current practices for shipping, receiving,
and storage of select agents and toxins to ensure that regulated
entities have consistent regulatory procedures for securing and
monitoring the shipment, receipt, and storage of these items. Some
commenters stated that codification of current practices for shipping,
receiving, and storage are unnecessary and recommended that the
provision be deleted. Other commenters recommended that we define and
clarify the term ``unexpected shipments.'' We made no changes to the
proposed regulation based on the comments since we believe the entity's
security plan should have documented processes to ensure select agents
and toxins are safeguarded against theft, loss, intentional release or
unauthorized access at all times, including when a select agent or
toxin is (1) ready to be packaged for transportation, (2) packaged for
shipment, or (3) received by a person with approval to access select
agents and toxins. These procedures would serve to decrease the chance
that such materials would be made available to an unauthorized
individual or an individual without a legitimate use for the materials.
We also believe that the term ``unexpected shipments'' is self-
explanatory and that an entity's security plan should contain
procedures for the handling of unexpected shipments (e.g., when an
entity receives a shipment of a select agent that it had neither
requested nor coordinated for, and therefore was not expecting).
Information Security
We proposed that the security plans of entities with select agents
and toxins must include provisions for information security. Many
commenters had questions or concerns regarding the additions to the
security plan proposed in section 11(c)(9) of the select agent
regulations. The commenters expressed concerns that the requirement
represents an added regulatory burden and the impact of this
requirement should be evaluated. Other commenters thought that persons
having access to information about select agents should not be
regulated as having access to the select agents. The commenters further
expressed their belief that the proposed language is vague and lacks
sufficient direction for securing the information. We agree with the
commenters. The purpose of the requirement in question is to clarify
section 11(c)(9)(i) of the regulation that requires the entity to have
procedures in place for information systems control. This is an
overarching requirement that covers electronic [information technology]
and non-electronic [hardcopy] information
[[Page 61099]]
oversight by the regulated community. Our intent was not to regulate
access to experimental data or the results of studies involving select
agents and toxins but to regulate access to the select agents and
toxins themselves. Therefore, we have revised the language in order to
clearly indicate that the information security provisions in question
should be for access to an entity's registered space and records
pertaining to select agents and toxins, as identified in sections 11
and 17 of this part.
Commenters expressed concerns that the new information security
requirements in section 11(c)(9)(ii) would require registration and
security risk assessments for all staff managing records pertaining to
select agent work. Our response is that this would depend on the
individual's duties. If an individual is able to access a select agent
or toxin, the individual would need to undergo a security risk
assessment. However, if the individual's duties are limited so that he
or she would be prevented from accessing the select agents or toxins,
then the individual would not need to undergo a security risk
assessment.
We anticipate that these requirements are already being met and
will merely require entities to document the systems and processes
currently in place. The guidance documents developed in conjunction
with this rule are, in part, a response to the questions and issues
raised by the commenters. Guidance on information security may be found
at www.selectagents.gov. Issues addressed in the guidance document
include, but are not limited to: information technology security,
network security, computer security, peripheral devices and data
storage, physical security and its application to information security,
risk management, and training.
Inventory Verification for Select Agents and Toxins
We proposed more specific minimum security standards for select
agents or toxins that included inventory verifications for select
agents and toxins. Commenters requested that section 11(e)(4)(ix) be
revised to delete the word ``all'' and clarify that the inventory
audits be conducted for only those affected Tier 1 select agents and
toxins. We agree with the commenters that the intent of the proposed
provision was limited to only those select agents and toxins affected
by the triggering event. However, we reevaluated the proposal that
would have been limited to only Tier 1 agents and toxins, and based on
experience, believe that this provision needs to be applied to all
select agents and toxins. Therefore, we have revised the final
regulatory language to address inventory verification for all select
agents and toxins, by creating a new subparagraph (e) in section 11
which states ``(e) Entities must conduct complete inventory audits of
all affected select agents and toxins in long-term storage when any of
the following occur:
(1) Upon the physical relocation of a collection or inventory of
select agents or toxins for those select agents or toxins in the
collection or inventory;
(2) Upon the departure or arrival of a principal investigator for
those select agents and toxins under the control of that principal
investigator; or
(3) In the event of a theft or loss of a select agent or toxin, all
select agents and toxins under the control of that principal
investigator.''
Reference
We proposed to remove the reference in Sec. 73.11(e), ``Laboratory
Security and Emergency Response Guidance for Laboratories Working with
Select Agents'' in Morbidity and Mortality Weekly Report (December 6,
2002) because we posted a security guidance document in March 2007 that
supersedes this reference. We received no comments regarding the
removing of this reference.
Reporting Incidents to the FBI
We proposed to add a requirement that the security plan include
procedures for the Responsible Official to immediately notify the FBI
of suspicious activity that may be criminal in nature and related to
the entity, its personnel, or its select agents or toxins. Commenters
stated that this proposal contradicts FBI guidance contained in their
``Agricultural, Chemical and Petroleum Industry Terrorism Handbook''
and creates a conflict within those entities that have their own
recognized law enforcement agencies. Commenters requested justification
for this change and clarification on the intent of the requirement.
Commenters also argued that the proposed language is unclear and
unnecessary. Specifically, commenters asked what constitutes a
``suspicious criminal activity''; what is an ``entity''; and whether
the intent of this proposal is for the Responsible Official to be the
designated individual to contact the FBI. We do not believe that there
exists any conflict between the security requirements in section 73.11
(Security) of the select agent regulations and the guidance contained
in the FBI's ``Agricultural, Chemical and Petroleum Industrial
Terrorism Handbook.'' However, where any conflict might exist, the
requirements of the federal regulations would supersede guidance. The
intent of this requirement is to facilitate the involvement of
antiterrorism resources which will increase the security of select
agents and toxins. We also believe that the FBI field offices, which
are centrally located in major metropolitan areas across the United
States, can assist the entity by working closely with them on crime
threats. However, we agree with the commenters that it may be
appropriate that the notification of suspicious activity first go to
the local law enforcement. Therefore, we have changed the language in
section 73.11(c)(8) to read: ``Describe procedures for how the
Responsible Official will be informed of suspicious activity that may
be criminal in nature and related to the entity, its personnel, or its
select agents or toxins; and describe procedures for how the entity
will notify the appropriate federal, state, or local law enforcement
agencies of such activity.'' The guidance document on reporting
suspicious activities may be found at www.selectagents.gov.
Intrusion Detection System
We proposed more specific minimum security standards for select
agents and toxins that included intrusion detection systems. Commenters
requested clarification as to what was meant by ``intrusion detection
system'' (IDS) and asked for examples of what constitutes an IDS. They
also requested clarification concerning the requirement that
``personnel monitoring the IDS must be capable of evaluating and
interpreting the alarm.'' We have made no changes in response to this
comment. We believe that the terms are self-explanatory and these types
of alarms need to be monitored by personnel who are capable of
responding appropriately. However, we are removing the words
``prescribe and/or'' to clarify the intent of the provision. We have
developed guidance that describes IDS as a sensor device or devices
which triggers an alarm when a security breach occurs and notifies a
response force (e.g., police, guards, etc.) capable of addressing any
threat that may be present. This guidance also provides examples of
various types of IDS. The guidance document may be found at
www.selectagents.gov.
Submission of Security Plans
We proposed to amend Sec. 73.11 to require that the entity
security plan be submitted for initial registration and renewals of
registration. Commenters recommended that we eliminate the proposed
requirement, and stated that
[[Page 61100]]
this requirement would delay the renewal process and place entities in
a ``regulatory bind,'' that the requirement would compromise the ``need
to know'' status of the security plans, and that these documents should
remain a protected document made available for review during the site
visit only. We made no changes to the regulations based on these
comments. Section 11 already has a provision that ``the security plan
must be submitted upon request.'' The requirement in question merely
codifies our long-standing policy of requesting the security plans for
initial registration and the renewal process. We also note that, in
practice, the submission of security plans for initial registration and
registration renewals has not created a delay in either process.
Security for Tier 1 Select Agents and Toxins
Access Controls to Tier 1 Agents
We proposed specific minimum security standards for access controls
to Tier 1 agents in section 11(4)(iii) of the regulations. One
commenter stated that these provisions would be difficult for
laboratories co-located with other entities. We made no changes to the
proposed standards based on this comment. Based on our experience with
over 350 entities in a ten-year period, we observed that registered
entities have been successful in meeting the current regulatory
requirements in a co-located situation, and we have no reason to
believe that this will not continue.
Back-Up Power for Tier 1 Select Agents and Toxins
We proposed more specific minimum security standards for Tier 1
agents that included the provision of back-up power. Commenters
requested clarification regarding whether the back-up power requirement
would only apply to registered spaces or whether it would include the
entire entity or building that houses the registered space. Commenters
recommended adding the phrase ``for the registered space'' into this
section. We agree with the commenters and have revised the language
accordingly.
Another commenter stated that the provision should remain a
recommendation not a requirement. Although we believe back-up power for
information security networks is an essential component for the
safeguarding of Tier 1 agents against unauthorized access, theft, loss,
or release during power outages, further consideration led us to alter
the nature of this requirement. Rather than focusing on power/
electricity alone, we have clarified the requirement in order to
address the importance of having comprehensive back-up procedures in
the event of a system failure. These procedures may include, but are
not limited to, provisions for back-up power.
Security Enhancements for Tier 1 Select Agents and Toxins
We proposed specific minimum security standards for Tier 1 select
agents or toxins. Commenters requested guidance and a timetable of when
the security upgrades need to be addressed. In this final rule, we have
included a phase-in period for the effective date for certain
requirements which should allow entities sufficient time to comply
without causing disruption or termination of research or educational
projects. As noted in the ``Effective Dates'' portion of this document,
one hundred and eighty days after the publication of the final rule,
entities will need to be in compliance with new provisions outlined in
section 11 (Security). In addition, we have developed guidance to
assist entities with security enhancements for Tier 1 agents.
Other commenters stated that the proposed rule included more
specific minimum security standards for Tier 1 select agents and toxins
and requested that we identify criteria for stratifying security
requirements, making them risk-based and considering the type of work
performed at the facility. The commenters also argued that the
additional regulations for Tier 1 agents and toxins will create more
responsibilities for the entity and require more resources to meet
these requirements. While we are in general agreement with these
concerns, we note that entities possessing Tier 1 agents and toxins are
already meeting these requirements. In addition, we have developed
guidance to assist entities with security enhancements for Tier 1
agents, which may be found at www.selectagents.gov. Therefore, we are
making no changes to the minimum security standards as proposed in the
NPRM.
Suitability Assessment for Access to Tier 1 Select Agents and Toxins
We proposed specific minimum security standards, including
personnel suitability assessments, for access to Tier 1 select agents
and toxins. Many commenters had questions or concerns regarding these
additional requirements, as described in section 11(f) of the proposed
rule. Specific additions addressed by the commenters included: Pre-
access suitability assessments, ongoing suitability assessments, and
self- and peer-reporting of incidents or conditions that could affect
an individual's ability to safely have access to or work with Tier 1
select agents and toxins. Commenters generally divided into two groups
in their response to the proposed additions. Some felt that the
requirements were too vague to prove useful and the requirements
created administrative burden without improving the overall security of
Tier 1 select agents and toxins. Others felt that the requirements
could or would require entities to behave in a manner contrary to local
laws, privacy laws, or union contracts. Commenters also felt that the
proposed language, ``individuals with access approval to select agents
and toxins are trustworthy and behaving in a manner that upholds public
health and safety, security, and the integrity of the scientific
enterprise'' were subjective standards that would be difficult to
enforce. We agreed with the commenters and revised the language in the
final rule to read that the security plan must contain procedures that
will limit access to a Tier 1 select agent or toxin to only those
individuals who are approved by the HHS Secretary or Administrator,
following a security risk assessment by the Attorney General, have had
an entity-conducted pre-access suitability assessment, and are subject
to the entity's procedures for ongoing suitability assessment.
We anticipate that these requirements are already being met at many
registered entities and will merely require those entities possessing a
Tier 1 select agent or toxin to formalize and document the systems and
processes currently in place. Therefore, we do not believe the
registered entities possessing a Tier 1 select agent or toxin will
endure additional significant costs for suitability assessments. We
believe that many of the specific concerns raised by commenters
regarding potential violation of laws or union contracts arose as a
result of the commenters' examination of the FESAP November 2, 2010
document entitled ``Recommendations Concerning the Select Agent
Program.'' As a matter of clarification, the Federal Select Agent
Program considered the FESAP recommendations as well as recommendations
from other sources (e.g., the National Science Advisory Board for
Biosecurity, the National Research Council, and the EO 13486 Working
Group), in developing the proposed rule provisions addressing personnel
suitability. While we have created specific guidance regarding this
[[Page 61101]]
section of the revised rule, we are leaving the regulations in their
broadly-written state in order to provide entities with flexibility in
meeting these requirements. Given our experience with the select agent
regulations and the wide variety of regulated entities those
regulations cover, we have found this to be the most effective
approach. The personnel suitability guidance document developed in
conjunction with this rule is, in part, a response to the questions and
issues raised by the commenters. Issues addressed in the guidance
document include, but are not limited to:
(1) Understanding the potential for insider threat;
(2) Understanding the needs for suitability assessments;
(3) Delineating the roles and responsibilities of individuals to
ensure optimal security;
(4) Requesting information about individuals in a standardized
manner and assessing individuals in the context of safety and security;
(5) Responding to reports in a consistent, prompt, and confidential
manner;
(6) Providing training for recognizing and reporting suspicious
behavior.
Full guidance on suitability assessments may be found at
www.selectagents.gov.
One commenter requested an exclusion or exemption clause for
entities that are registered to possess Tier 1 select agents or toxins,
but do not possess them. We made no changes to the regulations based on
this comment. Entities that are registered to possess, use or transfer
select agents and toxins must meet all of the regulatory requirements,
regardless of whether or not they actually possess these materials.
Security Training for Access to Tier 1 Select Agents and Toxins
We proposed specific minimum security standards, including security
training, for those individuals who would have access to Tier 1 select
agents or toxins. Commenters requested clarification whether training
of ``all entity employees'' mentioned in section 11(e)(2)(ii) meant
everyone in the facility or those ``Security Risk Assessment-approved
employees.'' We agree with the commenters and have revised the language
in the regulations to clarify that the training is for employees with
access to Tier 1 select agents and toxins.
Three Barriers for Tier 1 Select Agents and Toxins
We proposed specific minimum physical security standards for Tier 1
select agents or toxins that included a requirement for three barriers
protecting access to these materials. Commenters requested
clarification regarding what was meant by ``barrier'' and asked for
examples of what constitutes as a barrier. They also requested
clarification concerning the word ``delay'' since, according to the
commenters, the word does not seem to describe the needed function.
We agree with the commenters that the word barrier needed further
explanation and, in the definitions section in Sec. 73.1, we have
defined the term ``Security barrier'' as a physical structure that is
designed to prevent entry by unauthorized persons. In addition, we have
revised the language in this section to more clearly articulate that
entities possessing Tier 1 select agents and toxins must have a minimum
of three security barriers where each security barrier adds to the
delay in reaching secured areas where select agents and toxins are used
or stored. One of those security barriers must be monitored in such a
way as to detect intentional and unintentional circumventing of
established access control measures under all conditions (day/night,
severe weather, etc.). The final barrier must limit access to the
select agent or toxin to personnel approved by the HHS Secretary or
Administrator, following a security risk assessment by the Attorney
General.
Other commenters believed that the proposed requirement represents
an added expense. Although we agree that there are expenses associated
with the implementation of security measures, we do not anticipate that
significant additional expenditures will be necessary for registered
entities already possessing Tier 1 select agents or toxins. We have
developed guidance to assist entities with the security barrier
requirement, which may be found at www.selectagents.gov.
Response Time for Tier 1 Select Agents and Toxins
We proposed specific minimum security standards, including a
response time for security forces or local police that could not exceed
15 minutes from the time of an intrusion alarm or report of a security
incident in section 73.11(e)(4)(viii), for possessors of Tier 1 select
agents and toxins. Commenters questioned why a 15 minute response time
was chosen. Commenters also inquired whether there would be any
penalties if local law enforcement exceeds 15 minutes with their
response time. In addition, commenters stated that the proposed
definition of response time is unclear. One commenter recommended that
we revise the provision to read ``Response time for security forces or
local police must not exceed 15 minutes from the time of alerting the
designated force.''
Based on the comments received, we have modified the language of
this section. While retaining a 15-minute response time goal for
security forces or local police, we have provided flexibility for
entities to develop systems in line with the optimal achievable
response time in their area by revising the language to read: ``The
entity must: (A) Determine that the response time for security forces
or local police will not exceed 15 minutes or (B) Provide security
barriers that are sufficient to delay unauthorized access until the
response force arrives in order to safeguard the select agents and
toxins from theft, intentional release, or unauthorized access. The
response time is measured from the time of an intrusion alarm, or
report of a security incident, to the arrival of the responders at the
first security barrier.''
Our selection of the 15 minute response time metric is based on DOD
and DHS standards for high value assets (e.g., MD Number 11046 (Open
Storage Area Standards for Collateral Classified Information),
Department of Homeland Security Management Directive System MD) and
also on our analysis of incident response plans provided by registered
entities since 2003. The response time is measured from the time of an
intrusion alarm, or report of a security incident, to the arrival of
the responders at the first security barrier. A response is a force
capable of interrupting a threat and may be unarmed guards, armed
guards, or local law enforcement.
Security Requirements for Variola Major Virus or Variola Minor Virus
In recognition of the special public health risks associated with
Variola major virus and Variola minor virus, we proposed to require
additional physical security measures over and above those proposed for
Tier 1. Commenters were concerned about listing the Variola major virus
(smallpox virus) as a Tier 1 agent, given the stringent conditions
already in place for its handling and tracking. The commenters
recommended an alternative approach might be to designate the smallpox
virus as a pathogen with very special handling requirements, given that
smallpox has been officially eradicated worldwide.
[[Page 61102]]
We made no changes to the regulations based on the comment. We
believe that setting up a different special class of standards for one
pathogen would needlessly increase the complexity of the regulatory
provisions without any benefit of increased security. The requirements
designated for Tier 1 agents were meant for those 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. As such,
Variola major virus and Variola minor virus meet that criterion. We
also note that Variola major virus is a special case and that there are
additional, specific requirements for Variola major virus in addition
to the Tier 1 requirements. These specific requirements for Variola
major virus and Variola minor virus do not apply to the other Tier 1
agents.
One commenter requested clarification that requirements are not
applicable to diagnostic laboratories that may identify Variola major
virus or Variola minor virus during the course of routine work, but
would not otherwise ``possess'' these agents. We made no changes to the
regulations based on this comment. We note that the clinical and
diagnostic laboratory exemption found in section 5 of the regulations,
including all of the reporting and safeguarding requirements, remains
in effect.
Since the publication of the proposed rule, we became concerned
that the proposed requirement for all persons with access to the
Variola major or Variola minor virus to have a Top Secret clearance
would have the unintended effect of preventing HHS/CDC researchers from
being able to participate in collaborative work with international
colleagues, such as representative of the World Health Organization. To
address this concern, we have decided to modify the requirement to
require only personnel with independent unescorted access to Variola
major or Variola minor virus to have a Top Secret security clearance.
The requirements that any access to Variola major or Variola minor
would require approval from HHS/CDC and the approval of the Federal
Select Agent Program would remain in effect.
Biosafety Plan
One commenter was concerned that specifying the ``Biosafety in
Microbiological and Biomedical Laboratories'' (BMBL) (Ref 28)
publication in the regulatory text would in effect incorporate the
document by reference and therefore the BMBL should be published in the
Federal Register for public comment. We made no changes to the
regulations based on this comment. The BMBL has not been incorporated
by reference. The regulation clearly states that an individual or
entity should ``consider'' the BMBL when developing a site specific
biosafety plan. The BMBL is listed in the regulations because it
provides useful guidance for how to work safely with a variety of
pathogens. It also describes standard and special microbiological
practices, safety equipment, and facilities (constituting Biosafety
Levels 1-4). It is the document that is generally recognized as the
national biosafety standard in the United States.
Another commenter recommended that we clarify features of
containment infrastructure intended to facilitate biosafety of workers
dealing with these materials. The commenter recommended the regulatory
language read ``The biosafety plan must contain sufficient information
and documentation to describe the biosafety, physical and operational
containment requirements for working with the select agent or toxin
including any animals or plants intentionally or accidentally exposed
to or infected with a select agent.'' We made no changes to the
regulations based on this comment since we believe the proposed
language is clear and sufficient.
Another commenter recommended we remove the statement: ``The
occupational health program may also be made available to individuals
without access to Tier 1 select agents and toxins.'' We agree with the
commenter and have eliminated that portion of the regulatory text.
Occupational Health Program
We also proposed that the biosafety plan must include provisions
for the implementation of an occupational health program for
individuals with access to Tier 1 select agents and toxins. Many
commenters had questions and/or concerns regarding the addition of a
requirement for an occupational health program. Commenters generally
divided into two categories in their comments. Some commenters felt
that the requirement was too vague to prove useful and that the
requirement created an administrative burden without improving the
overall biosafety of Tier 1 select agents and toxins. Other commenters
indicated that the requirement could or would require entities to
behave in a manner contrary to Health Insurance Portability and
Accountability Act of 1996 (HIPAA). Commenters also felt that a
preventive health and post-exposure program is already available at
registered entities and should not be a requirement in the regulations.
We made no changes based on these comments.
While the select agent regulations do not supersede HIPAA, HIPAA
does not prevent the requirement of the establishment of an
occupational health program to address biosafety concerns for those
handling select agents and toxins.
We anticipate that this requirement is already being met and will
merely require those entities possessing a Tier 1 select agent or toxin
to codify and document the systems and processes currently in place.
Therefore, we do not believe registered entities possessing a Tier 1
select agent or toxin will endure significant additional costs
associated with an occupational health program. While we have created
specific guidance regarding this section, we are leaving the specifics
of the occupational health program as performance-based standards in
order to provide entities with flexibility in meeting these
requirements. We have found this to be the most effective approach
given the wide variety of regulated entities these regulations cover.
Full guidance on an occupational health program may be found at
www.selectagents.gov.
Restricted Experiments
We proposed to add language in order to expand the ``restricted
experiment'' approval requirement to include all experiments involving
the creation of drug resistant select agents that are not known to
acquire that resistance naturally, if such acquisition could compromise
the control of disease agents in humans, veterinary medicine, or
agriculture regardless of the method or technology used to create the
resistance. Previously, the restricted experiment language concerned
only those experiments involving recombinant nucleic acids.
The restricted experiment definition currently covers the
``deliberate transfer of a drug resistance trait to select agents that
are not known to acquire the trait naturally, if such acquisition could
compromise the use of the drug to control disease agents in humans,
veterinary medicine or agriculture.'' We have removed the phrase ``use
of the drug'' and modified the language in the last sentence to read
``deliberate transfer of a drug resistance trait to select agents that
are not known to acquire the trait naturally, if such acquisition could
compromise the control of disease agents in humans, veterinary medicine
or agriculture.'' We made this change because while the introduction of
a drug resistance trait would normally
[[Page 61103]]
eliminate that drug as a therapeutic option to control the disease,
there may be alternative drugs available to control the disease.
Therefore, the new definition reads as follows: Restricted experiments
are defined as: ``(1) experiments that involve the deliberate transfer
of, or selection for, a drug resistance trait to select agents that are
not known to acquire the trait naturally, if such acquisition could
compromise the control of disease agents in humans, veterinary
medicine, or agriculture;'' and ``(2) experiments involving the
deliberate formation of synthetic or recombinant nucleic acids
containing genes for the biosynthesis of select toxins lethal for
vertebrates at an LD[50] < 100 ng/kg body weight.''
It should be noted that restricted experiments are not prohibited
experiments. However, an entity must seek permission prior to the
initiation of a restricted experiment and receive approval from the
Administrator or HHS Secretary. Approval for the performance of a
restricted experiment or the possession of a product of a restricted
experiment may involve meeting additional safety and/or security
requirements as prescribed by the Federal Select Agent Program. Many
experiments that involve the deliberate transfer of a drug resistant
trait do not meet the definition of a restricted experiment because the
drug is not used to control disease in humans, veterinary medicine, or
agriculture. The Federal Select Agent Program encourages anyone who
intends to conduct a select agent experiment utilizing drug resistance
markers to submit that experiment for review so that they can be
advised on whether the experiment would be considered a restricted
experiment and require approval prior to its initiation.
One commenter stated that ``denial of restricted experiments is an
obstacle to the development of countermeasures instead of promoting
real biosecurity.'' We made no changes based on this comment. As
mentioned previously, many experiments that involve the deliberate
transfer of a drug resistant trait to a select agent do not meet the
definition of a restricted experiment because the drug is not used to
control disease in humans, veterinary medicine, or agriculture. The
rationale for requiring a heightened review of experiments that involve
introduction of a drug resistant trait to a select agent for
therapeutically useful antibiotics is ultimately out of concern that
what is made in the laboratory might not always remain in the
laboratory and therefore present a public health or agricultural risk.
For experimental protocols utilizing transient drug resistant traits,
it should be noted that mutants possessing those traits can be
maintained without removal of the trait and therefore pose a potential
risk to public health or agriculture. We therefore consider these
protocols to fall under the restricted experiment section of the
regulations.
Commenters also suggested aligning the restricted experiment
language with the ``NIH Guidelines for Research Involving Recombinant
DNA Molecules'' (NIH Guidelines) language that restricts and requires
approval for experiments with pathogens involving drug resistance for
therapeutically useful agents against that pathogen. We made no changes
based on these comments. The definition of a restricted experiment is
aligned with the NIH Guidelines and reads as ``* * * select agents that
are not known to acquire the resistance naturally, if such acquisition
could compromise the control of disease agents in humans, veterinary
medicine, or agriculture.'' We have not expanded the definition to
include the introduction of all drug resistant traits to a select agent
but only to those traits used to control disease in humans, veterinary
medicine, or agriculture.
Incident Response
One commenter argued that since the incident response plan must
fully describe the entity's response policies or procedures for failure
of intrusion detection or alarm system, the Federal Select Agent
Program should provide clarification as to what was meant by an
intrusion detection system (IDS) and examples of what constitutes IDS.
We have developed guidance that describes IDS as a sensor device or
devices which triggers an alarm when a security breach occurs and
notifies a response force (e.g., police, guards, etc.) capable of
addressing any threat that may be present. This guidance also provides
examples of various types of IDS. The guidance document may be found at
www.selectagents.gov.
One commenter recommended that instead of using the word ``etc.''
in section 14(b) they recommended that the section state, ``* * * and
emergencies such as fire, gas leak, explosion, power outage, and other
natural and man-made events.'' We agreed with the commenter and revised
the language.
While we did not propose any changes to section 73.14 (c)(6), a
commenter recommended that the language regarding planning and
coordination with local emergency responders be amended. Specifically,
the commenter believed that biosafety, as opposed to biosecurity needs,
would be better addressed if this provision read as follows: ``* * *
emergency responders, including local public health authorities.'' We
made no changes to the section based on the comment since the proposed
language would limit the concept to only public health authorities and
not agricultural health. Emergency responders can also include police,
fire and rescue service, and emergency medical service.
Training
We proposed to specify that the Responsible Official ensure
maintenance of training records since there was no particular person
designated as the entity's required record keeper, only that a training
record must be kept. We received no comments regarding this proposal.
We proposed to amend the regulations in 42 CFR 73.15 that contain
provisions of mandatory training for staff and visitors who work in or
visit areas where select agents or toxins are handled or stored to
provide security awareness and incident response training. Commenters
requested clarification concerning the required annual insider threat
awareness briefings for those entities possessing a Tier 1 select agent
or toxin as proposed in section 15(b) of the select agent regulations.
The commenters asked that the content of these threat awareness
briefings be made available to public health laboratories so that it
could then be specifically customized for various regions of the
country and include what are the minimum requirements, who the intended
audience is, and what documentation will be needed to satisfy the
requirement.
While we have created specific guidance regarding this section of
the revised regulations, the guidance does not take the form of a
prescriptive program. Given our experience with the select agent
regulations and the wide variety of entities those regulations cover,
we have found a broader approach to be most effective. The guidance
documents developed in conjunction with this rule are, in part, a
response to the questions and issues raised by the commenters. The
document regarding annual insider threat awareness briefings includes a
designated person to manage the assessment of laboratory personnel,
laboratorian involvement in threat mitigation, and behaviors of concern
as specific examples of best practices that we believe entities would
be well served in adopting. Full guidance on this and other issues may
be found at www.selectagents.gov.
[[Page 61104]]
One commenter proposed that the requirements for incident response
training should remain as currently written to only include safety
incident training via annual blood-borne pathogens, general safety,
biological hygiene, chemical hygiene, and lab specific select agent
training. We made no changes to the proposed requirement based on this
comment because we believe that incident response training needs to be
expanded so that personnel are trained in how to safeguard select
agents and toxins during natural emergencies and man-made disasters.
Commenters requested clarification that refresher training would
only be mandated when substantive changes are made to the plans
including what level of retraining would be required and whether
retraining would only be required for those areas of the plan that have
been amended. We made no changes to the proposed requirements based on
these comments. We believe that the regulatory language clearly states
that training will need to be provided when significant processes are
changed in the plan and that training will need to be provided to those
individuals who are affected by these changes in the plan.
One commenter recommended that we consider the staff time it will
take for visitor training. We made no changes to the proposed
requirement based on this comment. First, we believe that it is very
important that visitors receive the appropriate incidence response and
security awareness training to protect their personal safety while in
registered areas. We do not believe that the staff time needed to
fulfill this requirement will cause a significant increase in time and
effort when integrated into the current visitor training program.
One commenter requested clarification on the refresher training of
escorted personnel and visitors because the commenter believed that
refresher training is only required once a year, but does not happen
with visitors or escorted personnel. We agreed with the commenter and
have revised the language to read: ``Refresher training must be
provided annually for individuals with access approval from the HHS
Secretary or Administrator or at such time as the registered individual
or entity significantly amends its security, incident response, or
biosafety plans.''
Transfers
We proposed to clarify when ``transportation in commerce'' begins
and ends to better allow registered entities to adequately address
those situations when a select agent or toxin is (1) ready to be
packaged for transportation, (2) packaged for shipment, or (3) received
and handled by a person with approval to access select agents and
toxins. One commenter stated that the security of the package between
steps (2) packaged for shipment and (3) received and handled by a
person with approval to access select agents and toxins should be the
sole responsibility of the courier. We made no changes to the language
based on this comment. As stated in the preamble to the proposed rule,
``transportation in commerce'' begins when the select agent(s) or
toxin(s) are packaged for shipment and ready for receipt by a courier
and ends when the package is received by the intended recipient who is
an individual approved by the HHS Secretary or Administrator to have
access to select agents and toxins, following a security risk
assessment by the Attorney General.
Commenters believed that the new provision outlined in section
16(f) meant that all transfers must be made by an individual approved
by the HHS Secretary or Administrator to have access to select agents
and toxins, following a security risk assessment by the Attorney
General. We agreed with the commenters and revised the language to
state that after authorization is provided by USDA/APHIS or HHS/CDC,
the packaging of the select agent(s) and toxin(s) is performed by an
individual approved by the HHS Secretary or Administrator to have
access to select agents and toxins and is in compliance with all
applicable laws concerning packaging.
Records
We proposed to clarify the current language that an accurate,
current inventory needs to be maintained for each select agent that the
entity possesses including synthetic select agent organisms and any
animals or plants intentionally or unintentionally exposed to or
infected with a select agent (including number and species, location,
and appropriate disposition). Commenters argued that counting
individual vials of replicating biological agents is costly,
burdensome, and a major source of frustration for investigators. They
further claimed that there is widespread concern that both counting
vials and measuring volumes of individual vials are not effective means
of increasing security and wondered if there was another way to account
for inventory. Other commenters noted that animals infected with a
select agent are part of ongoing experimentation and are thus part of
working stocks rather than current inventory and requested
clarification on whether or not the term ``animal'' also included
``arthropods.''
We are making no changes to the regulations based on these
comments. While we are aware of the burden resulting from the
requirement to maintain an accurate and current inventory of each
select agent and toxin held in long-term storage, we believe this is an
essential element to establish security of select agents or toxins. We
recognize that it may still be possible for an insider to steal a
sample of an agent either from working stock or from an inventory
without being detected. However, if an entity has a robust inventory
management system, such incidents have a better chance of being
detected. To assist registered entities in meeting the requirements for
accurate inventories of materials in long term storage, we have
developed guidance that may be found at www.selectagents.gov.
It should be noted that while the volume measurements the commenter
references are required for inventories of select toxins, they are not
required in the case of inventory of select agents held in long-term
storage due, in part, to the points raised by the commenter. However,
we disagree with the commenter's assessment that measuring volume in
the case of select toxins and counting vials in general, as part of
required inventory tracking of both select agents and toxins for
registered entities, is not necessary.
We recognize that there has been some confusion between those
infected animals (including arthropods) and plants considered to be
``working stock'' and those considered to be ``inventory held in long
term storage.'' To that end, we have developed specific guidance that
will enable entities to better differentiate between these two
categories. This guidance is available at www.selectagents.gov.
In order to clarify our intent regarding ``working stock'' and
``inventory held in long term storage,'' as it relates to infected
animals and plants, we are revising paragraph (a)(2) in section 17 of
the select agent regulations to require 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) instead of an accurate, current inventory
of those animals or plants.
One commenter had concerns about tracking nucleic acids for
laboratories, which generate bacterial mutants and perform reverse
genetics. The commenter believed that this would be
[[Page 61105]]
incredibly time consuming, overly burdensome, and of no value. The
commenter argued that the theft of viral genetic elements would be less
useful to a person without scientific expertise and unnecessary for the
individual with the skills.
We made no changes to the regulations based on this comment. It
should be noted that not all recombinant material is regulated. The
scenarios described by this commenter would not involve regulated
nucleic acids. For example, bacterial genomes and viral genomes not
determined to be infectious are not subject to these regulations.
Additional guidance on this topic is available at www.selectagents.gov.
Administrative Review
We proposed to amend the regulations in 42 CFR 73.20 that addresses
the administrative review of an individual or entity's denial,
revocation, or suspension of registration or access approval.
Specifically, we proposed to modify the current regulations in order to
allow individuals more time to gather the necessary components of their
appeal following the denial, limitation, or revocation of access
approval. In addition, we proposed to remove the provision ``Where the
denial, revocation, or suspension of an individual's access approval is
based upon identification by the Attorney General, the request for
review will be forwarded to the Attorney General'' to provide
clarification that the decision regarding the appeal is determined by
the HHS Secretary. We received comments supporting these proposed
changes.
Guidance Documents
In the proposed rule, we specifically requested comment from the
regulated community and any other interested persons on the need for
and desirability of guidance documents that would serve to assist
regulated entities in meeting the requirements of regulations. We were
particularly interested in public comment regarding Web sites,
articles, or other sources that may be useful in developing such
guidance documents. We received a number of comments on the issue of
guidance which are discussed below. As these comments pertain to the
development of guidance documents and not to the regulations
themselves, we have made no regulatory changes as a result. Guidance
documents may be found at www.selectagents.gov.
Commenters stated that further sources of information, apart from
interaction with Federal Select Agent Program inspectors, should be
made available to assist regulated entities in implementing the
additional requirements. Other commenters urged that we develop
guidance as a collaborative effort with a variety of subject matter
experts both inside and outside the government.
We agreed with these comments and consulted with a wide variety of
contributors including HHS and USDA subject matter experts, a National
Science Advisory Board for Biosecurity report entitled ``Enhancing
Personnel Reliability among Individuals with Access to Select Agents''
(Ref 24), the National Academies Committee on Laboratory Security and
Personnel Reliability Assurance Systems for Laboratories Conducting
Research on Biological Select Agents and Toxins report entitled
``Responsible Research with Biological Select Agents and Toxins'' (Ref
25), the Report from the Executive Order 13486 Working Group on
Strengthening Laboratory Security in the United States (Ref 26), and a
report from the Defense Science Board Task Force on Department of
Defense Biological Safety and Security Program (Ref 27).
There exist a variety of ways for regulated entities to obtain
information from the Federal Select Agent Program. HHS/CDC and USDA/
APHIS may be contacted via email at [email protected] or
[email protected], respectively.
Guidance is also available at www.selectagents.gov. The Federal Select
Agent Program issues periodic email updates, which are sent to
Responsible Officials and alternate Responsible Officials at all
registered entities. We also hold workshops on various topics of
concern to the regulated community. Examples of past workshops have
discussed personnel reliability programs, security plans, preparing a
registration package, and the inspection process.
Miscellaneous
Coordination Between USDA/APHIS and HHS/CDC
One commenter expressed general support for the harmonization of
APHIS and CDC select agent regulations. The commenter stated that such
coordination could be further achieved via joint inspections of
registered entities. We are making no changes as a result of this
comment since it is outside the scope of this rulemaking.
The commenter further stated that language and definitions used in
the USDA/APHIS and HHS/CDC regulations should be consistent, citing
HHS/CDC's use of the term ``biosafety'' in 42 CFR 73.12 as compared to
the term ``biocontainment'' found in USDA/APHIS's regulations in 7 CFR
331.12.
Since the Federal Select Agent Program is jointly administered by
USDA/APHIS and HHS/CDC, we make every effort to achieve congruence
between our various regulations. In certain cases, as a result of the
differences between plant, animal and human select agents and toxins,
the terminology employed must necessarily differ. The term
``biocontainment'' is found in the USDA/APHIS regulations in 7 CFR
331.12 relating to Plant Protection and Quarantine (PPQ) select agents
and toxins while the term ``biosafety'' is found in the USDA/APHIS
regulations in 9 CFR 121.12 relating to Veterinary Services (VS) select
agents and toxins. ``Biosafety'' is the accurate term to describe
procedures relating to humans or animals. However, the term
``biocontainment'' is more appropriate for describing procedures
necessary to contain plant pathogens.
Animals or Plants Exposed to or Infected With Select Agents or Toxins
We proposed to require that security, biosafety, and incident
response plans include provisions to address the safeguarding of
animals or plants accidentally or intentionally exposed to or infected
with select agents against unauthorized access, theft, loss or release.
Commenters requested clarification about whether this requirement would
be limited to experimental plants and animals that are possessed by and
controlled by the registered entity. We made no changes to the
requirement based on these comments. An entity's security, biosafety,
and incident response plans should address any plants or animals within
the entity that may be exposed to a select agent, regardless of whether
or not the exposure was intentional or accidental.
Another commenter requested clarification on whether the term
``animal'' included arthropods. We made no changes based on this
comment as the term ``animal'' does include arthropods.
Cost
Commenters requested that we consider the indirect consequences of
continuing to include agents and toxins on the select agent list, the
negative effect of the proposed rule changes on the potential workforce
for select agent research, and the possibility that additional
regulations concerning Tier 1 select agents and toxins will mandate
more federal oversight and institutional
[[Page 61106]]
compliance requirements, resulting in increased costs to taxpayers both
directly and indirectly through reduced research efficiency. Commenters
requested that a full financial and scientific impact of these added
requirements be carefully assessed prior to implementation, especially
the increased costs to academic institutions with no associated
funding, and the increased burden on investigators already having
difficulty finding time for research and experimentation. The
commenters also stated that the timeline for implementation of the new
requirements should be considered and disclosed to affected entities.
A cornerstone of the Federal Select Agent Program is to establish
and enforce safety and security measures to prevent access to select
agents and toxins for use in domestic or international terrorism or for
any other criminal purpose. An equally important function of the
Federal Select Agent Program is to allow for the appropriate
availability of biological agents and toxins for research, education,
and other legitimate purposes. To achieve both requires the balancing
of the need for continuing biological research with requiring a level
of safety and security commensurate with the risks posed by these
biological agents and toxins. We understand that safety and security
requirements cost money and that money in the area of biological
research is often a scarce commodity. However, we are also aware that a
lack of adequate safety and security requirements could result in
damages measured both in dollars and in human lives. It is our
determination, based on the information available to us, that the
additional requirements would not constitute a significant economic or
recordkeeping burden on the regulated entities. We also believe that in
many cases these regulations serve to codify systems and procedures
already in use by a majority of regulated entities.
To achieve regulatory flexibility, we have included a phase-in
period for the effective date for certain requirements of the revised
regulations which should allow entities to comply without causing
disruption or termination of research or educational projects. As noted
in the ``Effective Dates'' portion of this document, sixty (60) days
from the publication of the final rule, entities will need to be in
compliance with sections 1-10, 13, 16, and 20. One hundred and eighty
days after the publication of the final rule, entities will need to be
in compliance with sections 11 (Security), 12 (Biosafety), 14 (Incident
response), and 15 (Training).
Request for a Letter of Interpretation Policy
One commenter suggested that the Federal Select Agent Program
should augment guidance documents with a letter of interpretation
policy. Specifically, the commenter recommended that select agent
registrants should be able to submit written requests detailing a
compliance issue and receive back a written letter of interpretation
from the Federal Select Agent Program in a similar manner as employers
can submit requests for interpretation to the Department of Labor
Occupational Safety and Health Administration. We are making no changes
to the select agent regulations based on this comment because it is
outside the scope of this rule.
III. Required Regulatory Analyses
A. Executive Orders 12866 and 13563
Executive Orders 12866 and 13563 direct agencies to assess all
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety effects, distributive impacts, and equity). Executive
Order 13563 emphasizes the importance of quantifying both costs and
benefits, of reducing costs, of harmonizing rules, and of promoting
flexibility.
Under Executive Order 12866, HHS must determine whether a
regulatory action is ``significant.'' A ``significant regulatory
action'' under Executive Order 12866 is defined as (1) an action that
is likely to result in a rule that may have an annual effect on the
economy of $100 million or more, or adversely and materially affects a
sector of the economy, productivity, competition, jobs, the
environment, public health or safety, or state, local or tribal
governments or communities (or an economically significant action); (2)
creates a serious inconsistency or otherwise interferes with an action
taken or planned by another agency; (3) materially alters the budgetary
impact of entitlements, grants, user fees or loan programs or the
rights and obligations of recipients; or (4) raises novel legal or
policy issues. Because this rulemaking proposes changes to how a subset
of select agents and toxins is protected, this rule has been determined
to be ``significant'' under Executive Order 12866 and, therefore, has
been reviewed by the Office of Management and Budget (OMB).
We have prepared an economic analysis for this rule. The economic
analysis provides a cost-benefit analysis, as required by Executive
Order 12866, and a final regulatory flexibility analysis (See Section
III.B. of this Preamble) that 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 on www.regulations.gov, Docket CDC-
2012-0012, at www.select agents.gov or by contacting the person listed
under FOR FURTHER INFORMATION CONTACT.
Summary of the Regulatory Impact Analysis
The Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (Pub. L. 107-188) provides for the regulation of
certain biological agents and toxins that have the potential to pose a
severe threat to human, animal, or plant health, or to animal or plant
products. The Animal and Plant Health Inspection Service (APHIS) and
the Centers for Disease Control and Prevention (CDC) have primary
responsibility for implementing the provisions of the Act within the
Department of Agriculture and the Department of Health and Human
Services, respectively. Within APHIS, Veterinary Services (VS) select
agents and toxins are those that have been determined to have the
potential to pose a severe threat to animal health or animal products,
and Plant Protection and Quarantine (PPQ) select agents and toxins are
those that have been determined to have the potential to pose a severe
threat to plant health or plant products. HHS select agents and toxins
are those that have been determined to have the potential to pose a
severe threat to human health. USDA/APHIS and HHS/CDC coordinate
regulatory activities for overlap select agents and toxins that have
been determined to pose a severe threat to human and animal health or
animal products.
Sections 201 and 212(a)(2) of the Act require a biennial review and
republication of the select agent and toxin list, with revisions as
appropriate in accordance with this law. These final rules will
implement the recommendations of the third biennial review, and
incorporate risk-based tiering of the select agent and toxin lists, as
required by Executive Order 13546, ``Optimizing the Security of
Biological Select Agents and Toxins in the United States.'' In
addition, the APHIS and CDC final rules will codify several amendments
to the regulations, including the addition of definitions and
clarification of language concerning security, training, biosafety/
[[Page 61107]]
biocontainment, and incident response. These changes will improve the
applicability and effectiveness of the select agent regulations and
provide for enhanced program oversight.
Based on information obtained through site-specific inspections, we
believe most registered entities already have in place many of the
information security requirements set forth in the final rules, and
compliance costs of the rules are therefore expected to be minimal.
Entities more likely to be affected will be laboratories and other
institutions conducting research and related activities that involve
the use of select agents and toxins categorized as Tier 1. These
entities will be required to conduct a pre-access suitability
assessment of individuals with access to a Tier 1 select agent or
toxin, as well as enroll these individuals in an occupational health
program.
The rules would reduce the period that FBI background checks are
valid from five to three years. This increased frequency would
effectively increase the cost of background checks by 67 percent. Based
on the current number of individuals required to have the background
checks, we estimate that the present value of these government-borne
costs over five years will increase by $1.96 million across all
registered entities. The annual increase in costs will total about
$432,000.
While we expect few if any of the registered entities to incur
significant compliance costs, required documentation of measures
already regularly performed with respect to biocontainment/biosafety,
incident response, information security, and ongoing suitability
assessment may require additional time of personnel. We estimate
additional recurring costs related to information security, such as for
software updates, could total about $2 million per year, or about
$5,500 per entity, in the unlikely event that none of the entities
already uses equivalent information security measures. As noted, many
of these costs are already currently borne by entities in their conduct
of generally recognized best practices. For entities possessing a Tier
1 agent or toxin, the costs of pre-access suitability assessments and
occupational health programs are estimated to total between $2.8
million and $4.4 million, or between about $9,600 and $15,100 per
entity, on average. Again, actual costs incurred are unlikely to reach
these maximum cost ranges; we expect that many of the entities with a
Tier 1 agent or toxin already conduct assessments and have health
programs similar or equivalent to those required by the final rules.
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 amended regulations will enhance the protection of human,
animal, and plant health and safety. The final rules will 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.
Summary of the Estimated Maximum Additional Costs Attributable to the Final Rules for the Federal Government and
Affected Entities \1\
----------------------------------------------------------------------------------------------------------------
Unit cost Number of units Total additional cost
----------------------------------------------------------------------------------------------------------------
Added Annual Cost for the Federal Government
----------------------------------------------------------------------------------------------------------------
Increased frequency of FBI/CJIS $240 per person........ 13,488 approved SRAs; $432,000 per year \2\.
background checks. checks valid for three
years.
----------------------------------------------------------------------------------------------------------------
Added Recurring Costs for Affected Entities \3\
----------------------------------------------------------------------------------------------------------------
Submission of Security Plan.......... $4.95 per submission.. Estimated 130 annual $643.50 per year.
renewals.
Information Security \4\
network connectivity monitoring $24-$37 per license.... 365 registered entities $8,760-$13,505 per
(encryption software). licensing period.
network connectivity monitoring $79-$199 per license... 365 registered entities $28,835-$72,635 per
(firewall software). licensing period.
malware software \4\ (intrusion $15 per computer....... 365 registered entities $5,475 per software
detection). update.
malware software (antivirus)..... $80 per user per year.. 13,488 approved SRAs... $1,079,040 per year.
system software updates $2,400 per year........ 365 registered entities $876,000 per year.
(dedicated time for IT
Specialist).
----------------------------------------------------------------------------------------------------------------
Total \5\.................... approximately $2 million annually, or on average about $5,500 per
registered entity.
----------------------------------------------------------------------------------------------------------------
Added Costs for Entities that have a Tier 1 Select Agent or Toxin 3,6
----------------------------------------------------------------------------------------------------------------
Pre-suitability Assessment........... $100-$120 per person... 13,488 approved SRAs... $1.35-1.62 million.
Occupational Health Program.......... $107-$204 per person... 13,488 approved SRAs... $1.44-2.75 million.
----------------------------------------------------------------------------------------------------------------
[[Page 61108]]
Total \7\.................... approximately $2.8 million-$4.4 million, or on average about $9,600-
$15,100 per entity with a Tier 1 agent or toxin
----------------------------------------------------------------------------------------------------------------
\1\ The costs for registered entities summarized in this table are the estimated maximum additional expenditures
that would be incurred, if none of the entities currently meets any of the additional security requirements
set forth in the final rules. In addition, there will be the opportunity cost of additional time required to
modify biosecurity and incident response plans and to conduct audits. Entities will be required to conduct
complete inventory audits of all select agents and toxins in long-term storage upon the physical relocation of
a collection or inventory of select agents or toxins, upon the departure or arrival of a principal
investigator for those select agents or toxins, or in the event of a theft or loss of a select agent or toxin.
Time costs are noted qualitatively in the Benefits and Costs section of this analysis.
\2\ The annual additional cost estimate assumes a uniform distribution of the 13,488 background checks over
three years.
\3\ Based on site inspections, many of the entities currently have provisions in place similar or equivalent to
those required.
\4\ Several of the recurring costs are associated with technological updating of information security, such as
firewall and malware software updates. Estimated costs across all entities are uncertain as information is
unavailable regarding the number of computers per affected entity. The estimates assume a single computer per
entity is used for covered work.
\5\ Assumes costs of licensing and software updates are incurred annually.
\6\ Estimated costs are likely overstated as not all SRA-approved individuals will have access to Tier 1 select
agents and toxins.
\7\ Average cost per entity is based on 292 entities that are registered to possess a Tier 1 agent or toxin.
B. Regulatory Flexibility Act
The Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.)
requires an agency to consider the potential impact of its regulations
on small entities, including small businesses, small governmental
units, and small not-for-profit organizations. We have prepared an
economic analysis for this rule. The economic analysis provides a cost-
benefit analysis, as required by Executive Order 12866, and a final
regulatory flexibility analysis that examines the potential economic
effects of this rule on small entities, as required by the Regulatory
Flexibility Act. Based on the economic analysis, which is available at
www.selectagents.gov, we do not expect the rule to have a significant
economic impact on small entities. In the absence of significant
economic impacts, we have not identified alternatives that would
minimize such impacts.
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.), the information collection or
recordkeeping requirements included in this final rule will be reviewed
by the Office of Management and Budget (OMB) as a revision to existing
OMB Control Number 0920-0576, expiration 10/31/2014.
USDA/APHIS and HHS/CDC are asking OMB to approve, for 3 years, the
use of these information collections, associated with its efforts to
more closely regulate select agents or toxins that could be used to
commit acts of domestic or international terrorism. We are soliciting
comments from the public (as well as affected agencies) concerning this
information collection activity. USDA/APHIS and HHS/CDC need this
outside input to help accomplish the following:
(1) Evaluate whether the proposed information collection is
necessary for the proper performance of our agency's functions,
including whether the information will have practical utility;
(2) Evaluate the accuracy of our estimate of the burden of the
proposed information collection, including the validity of the
methodology and assumptions used;
(3) Enhance the quality, utility, and clarity of the information to
be collected; and
(4) Minimize the burden of the information collection on those who
are to respond (such as through the use of appropriate automated,
electronic, mechanical, or other technological collection techniques or
other forms of information technology; e.g., permitting electronic
submission of responses).
Estimate of burden: Public reporting burden for this collection of
information is estimated to average 2.3187883 hours per response.
Respondents: Researchers, universities, research and development
organizations, commercial manufacturers, non-profit institutions,
diagnostic laboratories and other interested parties who possess, use,
or transfer agents or toxins deemed a severe threat to human, animal or
plant health, or to animal or plant products.
Estimated annual number of respondents: 386.
Estimated annual number of responses per respondent: 12.
Estimated annual number of responses: 4,721.
Estimated total annual burden on respondents: 10,947 hours. (Due to
averaging, the total annual burden hours may not equal the product of
the annual number of responses multiplied by the reporting burden per
response.)
----------------------------------------------------------------------------------------------------------------
Average
Number of Number of burden per Total burden
Section Form name respondents responses per response (in hours
respondent hours)
----------------------------------------------------------------------------------------------------------------
9 CFR 121.5 and 6, 7 CFR Report of 161 3 1 299
331.5, 43 CFR 73.5 and 6. Identification
of a Select
Agent or Toxin.
Sec. 121.7, Sec. 331.7, Application for 7 1 5 35
Sec. 73.7. Registration.
Sec. 121.7, Sec. 331.7, Amendment to a 380 7 1 2,660
Sec. 73.7. Certificate of
Registration.
Sec. 121.11, Sec. 331.11, Security Plan... 380 1 5 1,900
Sec. 73.11.
Sec. 121.12, Sec. 331.12, Biosafety/ 380 1 8 3,040
Sec. 73.12. Biocontainment
Plan.
Sec. 121.13, Sec. 331.13, Request 160 1 2 320
Sec. 73.13. Regarding a
Restricted
Experiment.
Sec. 121.14, Sec. 331.14, Incident 380 1 5 1,900
Sec. 73.14. Response Plan.
Sec. 121.15, Sec. 331.15, Training........ 380 1 1 380
Sec. 73.15.
[[Page 61109]]
Sec. 121.16, Sec. 331.16, Request to 290 1 2 580
Sec. 73.16. Transfer Select
Agents and
Toxins.
Sec. 121.17, Sec. 331.17, Records......... 295 1 0.5 148
Sec. 73.17.
Sec. 121.19, Sec. 331.19, Notification of 195 1 2 390
Sec. 73.19. Theft, Loss, or
Release.
----------------------------------------------------------------------------------------------------------------
Copies of this information collection may be obtained by calling
the CDC Reports Clearance Officer at (404) 639-5960 or sending an email
to [email protected]. HHS/CDC is requesting continued OMB approval to collect
this information through the use of five updated forms. These forms
are: (1) Application for Registration, (2) Transfer of Select Agent or
Toxin Form, (3) Facility Notification of Theft, Loss, or Release Form,
(4) Clinical and Diagnostic Laboratory Reporting Form, and (5) Request
for Exemption.
D. Executive Order 12988: Civil Justice Reform
This rule has been reviewed under Executive Order 12988, Civil
Justice Reform. Once the final rule is in effect: (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. Executive Order 13132: Federalism
This rule has been reviewed under Executive Order 13132,
Federalism. The review reveals that this regulation will not have
substantial and direct effects on Tribal governments and will not have
significant Tribal implications.
F. Plain Writing Act of 2010
Under Public Law 111-274 (October 13, 2010), HHS has attempted to
use plain language in promulgating the rule consistent with the Plain
Writing Act guidelines.
IV. References
1. Delgado, Erickson, et al., 2008. Chapare virus, a newly discovered
arenavirus isolated from a fatal hemorrhagic fever case in Bolivia.
PLoS Pathogens 4:e1000047.
2. Briese T, Paweska JT, McMullan LK, Hutchison SK, Street C, Palacios
G, Khristova ML, Weyer J, Swanepoel R, Egholm M, Nichol ST, Lipkin WI.
Genetic detection and characterization of Lujo virus, a new hemorrhagic
fever-associated arenavirus from southern Africa. PLoS 2009 May;
5(5):e1000455. Epub 2009 May 29. Available at www.plospathogens.org.
3. World Health Organization. Summary of probable SARS cases with onset
of illness from 1 November 2002 to 31 July 2003 [monograph on the
Internet]. 2003 Dec 31 [cited 2004 Aug 26]. Available from http://www.who.int/csr/sars/country/table2004_04_21/en/
4. World Health Organization. SARS case in laboratory worker in Taiwan,
China [monograph on the Internet]. 2003 Dec 17 [cited 2004 Aug 26].
Available from http://www.who.int/mediacentre/releases/2003/np26/en/
5. World Health Organization. China confirms SARS infection in another
previously reported case: summary of cases to date--Update 5 [monograph
on the Internet]. 2004 Apr 30 [cited 2004 Aug 26]. Available from
http://www.who.int/csr/don/2004_04_30/en/
6. World Health Organization. China's latest SARS outbreak has been
contained, but biosafety concerns remain--Update 7 [monograph on the
Internet]. 2004 May 18. Available from http://www.who.int/csr/don/2004_05_18a/en/index.html
7. Liang, G., Chen, Q., Xu, J., Liu, Y., Lim, W., Peiris, J. S.,
Anderson, L. J., Ruan, L., Li, H., Kan, B., et al. Laboratory diagnosis
of four recent sporadic cases of community-acquired SARS, Guangdong
Province, China. (2004) Emerg. Infect. Dis. 10, 1774-1781.
8. Sayeed et al. Epsilon-toxin is required for most Clostridium
perfringens type D vegetative culture supernatants to cause lethality
in the mouse intravenous injection model. Infect Immun. 2005
Nov;73(ll):7413-21
9. Favreau P, Krimm I, Le Gall F, Bobenrieth MJ, Lamthanh H, Bouet F,
Servent D, Molgo J, M[eacute]nez A, Letourneux Y, Lancelin JM.
Biochemical Characterization and Nuclear Magnetic Resonance Structure
of Novel [alpha]-Conotoxins Isolated from the Venom of Conus consors.
Biochemistry. 1999 May 11;38(19):6317-26
10. Groebe DR, Dumm JM, Levitan ES, Abramson SN. alpha-Conotoxins
selectively inhibit one of the two acetylcholine binding sites of
nicotinic receptors. Mol Pharmacol. 1995 Jul;48(1):105-11.
11. Groebe DR, Gray WR, Abramson SN. Determinants Involved in the
Affinity of [alpha] -Conotoxins GI and SI for the Muscle Subtype of
Nicotinic Acetylcholine Receptors. Biochemistry. 1997 May
27;36(21):6469-74.
12. Liu L, Chew G, Hawrot E, Chi C, Wang C. Two potent alpha3/5
conotoxins from piscivorous Conus achatinus. Acta Biochim Biophys Sin
(Shanghai). 2007 Jun; 39(6):438-44.
13. Acetylcholine Receptor Binding-Characteristics of Snake and Cone
Snail Venom Postsynaptic Neurotoxins: Further Studies with a Non-
radiological Assay. Bradley G. Stiles. Toxicon. 1993 Jul;31(7):825-34.
14. Galgiani, J.N. 1999. Coccidiomycosis: a regional disease of
national importance. Ann Intern. Med. 130:293-298.
15. Chen N., et al. 2005. Virulence differences between monkeypox virus
isolates from West Africa and the Congo basin. Virology 340:46-63.
16. Hutson C. L., et al. 2009. A prairie dog animal model of systemic
orthopoxvirus disease using West African and Congo Basin strains of
monkeypox virus. J. Gen. Virol. 90:323-333.
17. Saijo M., et al. 2009. Virulence and pathophysiology of the Congo
Basin and West African strains of monkeypox virus in non-human
primates. J. Gen. Virol. 90:2266-2271.
18. Sbrana E., Xiao S. Y., Newman P. C., Tesh R. B. 2007. Comparative
pathology of North American and central African strains of monkeypox
virus in a ground squirrel model of the disease. Am. J. Trop. Med. Hyg.
76:155-164.
19. Likos AM, Sammons SA, Olson VA, Frace AM, Li Y, Olsen-Rasmussen M,
Davidson W, Galloway R,
[[Page 61110]]
Khristova ML, Reynolds MG, Zhao H, Carroll DS, Curns A, Formenty P,
Esposito JJ, Regnery RL, Damon IK. A tale of two clades: monkeypox
viruses. J Gen Virol. 2005 Oct; 86(Pt 10):2661-72.
20. Azad and Radulovic, 2003: Azad AF, Radulovic S Pathogenic
rickettsiae as bioterrorism agents. Ann N Y Acad Sci. 2003; 990: 734--
738.
21. Gres[iacute]kov[aacute] M, Kaluzov[aacute] M, 1997. Biology of
tick-borne encephalitis virus. Acta Virol. Apr;41(2):115-24.
22. Ecker M, Allison SL, Meixner T, Heinz FX, 1999. Sequence analysis
and genetic classification of tick-borne encephalitis viruses from
Europe and Asia. J Gen Virol. Jan;80 (Pt 1):179-85.
23. Raoult D, Houpikian P, Tissot DH, Riss JM, Arditi-Djiane J, Brouqui
P. Treatment of Q fever endocarditis: comparison of 2 regimens
containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern
Med. 1999;159(2):167-73
24. National Science Advisory Board for Biosecurity report: ``Enhancing
Personnel Reliability among Individuals with Access to Select Agents''
(http://oba.od.nih.gov/biosecurity/meetings/200905T/NSABB%20Final%20Report%20on%20PR%205-29-09.pdf).
25. Responsible Research with Biological Select Agents and Toxins,
Committee on Laboratory Security and Personnel Reliability Assurance
Systems for Laboratories Conducting Research on Biological Select
Agents and Toxins, National Research Council of the National Academies
(http://www8.nationalacademies.org/cp/projectview.aspx?key=49097).
26. Report of the Working Group on Strengthening the Biosecurity of the
United States, Executive Order 13486 Working Group (http://edocket.access.gpo.gov/2009/pdf/E9-818.pdf).
27. Defense Science Board Task Force on Department of Defense
Biological Safety and Security Program (http://www.acq.osd.mil/dsb/reports/ADA499977.pdf).
28. Biosafety in Microbiological and Biomedical Laboratories (http://www.cdc.gov/biosafety/publications/bmbl5/index.htm).
List of Subjects in 42 CFR Part 73
Biologics, Packaging and containers, Penalties, Reporting and
recordkeeping requirements, Transportation.
Dated: September 28, 2012.
Kathleen Sebelius,
Secretary.
For the reasons stated in the preamble, the Centers for Disease
Control and Prevention, United States Department of Health and Human
Services, amends 42 CFR part 73 as follows:
PART 73--POSSESSION, USE, AND TRANSFER OF 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. Add Sec. 73.0 to read as set forth below.
Sec. 73.0 Applicability and related requirements.
All individuals and entities that possess SARS-CoV, Lujo virus, or
Chapare virus must provide notice to CDC regarding their possession of
SARS-CoV, Lujo virus, or Chapare virus on or before November 5, 2012.
Currently registered individuals and entities possessing SARS-CoV, Lujo
virus, or Chapare virus must meet all the requirements of this part by
December 4, 2012. All previously unregistered individuals and entities
possessing SARS-CoV, Lujo virus, or Chapare virus must meet all of the
requirements of this part by April 3, 2013.
0
3. Section 73.1 is amended by adding, in alphabetical order,
definitions of Conotoxins, Information security, Occupational exposure,
Recombinant nucleic acids, Security barrier, and Synthetic nucleic
acids to read as set forth below.
Sec. 73.1 Definitions.
* * * * *
Conotoxins means short, paralytic alpha conotoxins containing the
following amino acid sequence
X1CCX2PACGX3X4X5X
6CX7, whereas:
(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;
(2) The consensus sequence includes known toxins [alpha]-MI and
[alpha]-GI (shown above) as well as [alpha]-GIA, Ac1.1a, [alpha]-
CnIA, [alpha]-CnIB;
(3) X1 = any amino acid(s) or Des-X;
(4) X2 = Asparagine or Histidine;
(5) P = Proline;
(6) A = Alanine;
(7) G = Glycine;
(8) X3 = Arginine or Lysine;
(9) X4 = Asparagine, Histidine, Lysine, Arginine,
Tyrosine, Phenylalanine or Tryptophan;
(10) X5 = Tyrosine, Phenylalanine, or Tryptophan;
(11) X6 = Serine, Threonine, Glutamate, Aspartate,
Glutamine, or Asparagine;
(12) X7 = Any amino acid(s) or Des X; and
(13) ``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.
* * * * *
Information security means protecting information and information
systems from unauthorized access, use, disclosure, disruption,
modification, or destruction in order to provide--
(1) Integrity, which means guarding against improper information
modification or destruction, and includes ensuring information
authenticity;
(2) Confidentiality, which means preserving authorized restrictions
on access and disclosure, including means for protecting personal
privacy and proprietary information; and
(3) Availability, which means ensuring timely and reliable access
to and use of information.
Occupational exposure means any reasonably anticipated skin, eye,
mucous membrane, parenteral contact, or respiratory aerosol exposure to
select agents or toxins that may result from the performance of an
employee's duties.
* * * * *
Recombinant nucleic acids means:
(1) Molecules that are constructed by joining nucleic acid
molecules and that can replicate in a living cell or
(2) Molecules that result from the replication of those described
in paragraph (1) of this definition.
* * * * *
Security barrier means a physical structure that is designed to
prevent entry by unauthorized persons.
* * * * *
Synthetic nucleic acids means:
(1) Molecules that are chemically or by other means synthesized or
amplified, including those that are chemically or otherwise modified
but can base pair with naturally occurring nucleic acid molecules
(i.e., synthetic nucleic acids) or
(2) Molecules that result from the replication of those described
in paragraph (1) of this definition.
* * * * *
0
4. Section 73.3 is amended as follows:
0
a. By adding a sentence to the end of paragraph (a) to read as set
forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. In paragraph (c) introductory text, by adding the phrase ``and/or
Synthetic'' after the word ``Recombinant'' each time it appears.
[[Page 61111]]
0
d. In paragraph (c)(2) introductory text, by adding the phrase ``and/or
synthetic'' after the word ``Recombinant.''
0
e. By revising paragraph (d)(3) to read as set forth below.
0
f. By adding a new paragraph (d)(4) to read as set forth below.
0
g. By adding a new paragraph (d)(5) to read as set forth below.
0
h. By revising paragraph (e) to read as set forth below.
0
i. In paragraph (f)(3)(i), by removing the words ``Lassa fever virus''
and ``South American Haemorrhagic Fever virus (Junin, Machupo, Sabia,
Flexal, Guanarito)'' and by adding, after ``Botulinum neurotoxins,'',
the term ``Botulinum neurotoxin producing species of Clostridium.''
Sec. 73.3 HHS select agents and toxins.
(a) * * * The select agents and toxins marked with an asterisk (*)
are designated as Tier 1 select agents and toxins and are subject to
additional requirements as listed in this part.
(b) HHS select agents and toxins:
Abrin
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Conotoxins (Short, paralytic alpha conotoxins containing the following
amino acid sequence
X1CCX2PACGX3X4X5X
6CX7)
Coxiella burnetii
Crimean-Congo haemorrhagic fever virus
Diacetoxyscirpenol
Eastern Equine Encephalitis virus
Ebola virus*
Francisella tularensis*
Lassa fever virus
Lujo virus
Marburg virus*
Monkeypox virus
Reconstructed replication competent forms of the 1918 pandemic
influenza virus containing any portion of the coding regions of all
eight gene segments (Reconstructed 1918 Influenza virus)
Ricin
Rickettsia prowazekii
SARS-associated coronavirus (SARS-CoV)
Saxitoxin
South American Haemorrhagic Fever viruses:
Chapare
Guanarito Junin
Machupo
Sabia
Staphylococcal enterotoxins (subtypes A-E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
Far Eastern subtype
Siberian subtype
Kyasanur Forest disease virus
Omsk haemorrhagic fever virus
Variola major virus (Smallpox virus) *
Variola minor virus (Alastrim) *
Yersinia pestis *
* * * * *
(d) * * *
(3) Except as required in Sec. 73.16(l), the aggregate amount of
the toxin under the control of a principal investigator, treating
physician or veterinarian, or commercial manufacturer or distributor
does not, at any time, exceed the following amounts: 100 mg of Abrin;
0.5 mg of Botulinum neurotoxins; 100 mg of Conotoxins (Short, paralytic
alpha conotoxins containing the following amino acid sequence
X1CCX2PACGX3X4X5X
6CX7); 1,000 mg of Diacetoxyscirpenol; 100 mg of
Ricin; 100 mg of Saxitoxin; 5 mg of Staphylococcal enterotoxins
(subtypes A-E); 1,000 mg of T-2 toxin; or 100 mg of Tetrodotoxin.
(i) The amounts are transferred only after the transferor uses due
diligence and documents that the recipient has a legitimate need (i.e.,
reasonably justified by a prophylactic, protective, bona fide research,
or other peaceful purpose) to handle or use such toxins.
Notwithstanding the provisions of paragraph (d) of this section, the
HHS Secretary retains the authority to, without prior notification,
inspect and copy or request the submission of the due diligence
documentation to the CDC.
(ii) Reports to CDC if they detect a known or suspected violation
of Federal law or become aware of suspicious activity related to a
toxin listed in this part.
(4) An animal inoculated with or exposed to an HHS select toxin.
(5) Any South American genotypes of Eastern Equine Encephalitis
Virus and any West African Clade of Monkeypox virus provided that the
individual or entity can verify that the agent is within the exclusion
category.
(e) An attenuated strain of a select agent or an inactive form of a
select toxin may be excluded from the requirements of this part based
upon a determination by the HHS Secretary that the attenuated strain or
inactivated toxin does not pose a severe threat to public health and
safety.
(1) To apply for exclusion, an individual or entity must submit a
written request and supporting scientific information. A written
decision granting or denying the request will be issued. An exclusion
will be effective upon notification to the applicant. Exclusions will
be listed on the National Select Agent Registry Web site at http://www.selectagents.gov/.
(2) If an excluded attenuated strain or inactivated toxin is
subjected to any manipulation that restores or enhances its virulence
or toxic activity, the resulting select agent or toxin will be subject
to the requirements of this part.
* * * * *
0
5. Section 73.4 is amended as follows:
0
a. By adding a sentence to the end of paragraph (a) to read as set
forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. In paragraph (c) introductory text, by adding the phrase ``and/or
Synthetic'' after the word ``Recombinant'' each time it appears.
0
d. In paragraph (c)(2) introductory text, by adding the phrase ``and/or
synthetic'' after the word ``Recombinant.''
0
e. By adding a new paragraph (d)(3) to read as set forth below.
0
f. By revising paragraph (e) to read as set forth below.
0
g. In paragraph (f)(3)(i), by removing the words ``Brucella melitensis,
Hendra virus, Nipah virus, Rift Valley fever virus, and Venezuelan
equine encephalitis virus'' and adding, after ``Bacillus anthracis'',
the terms ``Burkholderia mallei'' and ``Burkholderia pseudomallei'' in
their place.
Sec. 73.4 Overlap select agents and toxins.
(a) * * * The select agents and toxins marked with an asterisk (*)
are designated as Tier 1 select agents and toxins and are subject to
additional requirements as listed in this part.
(b) Overlap select agents and toxins:
Bacillus anthracis*;
Bacillus anthracis (Pasteur strain);
Brucella abortus;
Brucella melitensis;
Brucella suis;
Burkholderia mallei*;
Burkholderia pseudomallei*;
Hendra virus;
Nipah virus;
Rift Valley fever virus;
Venezuelan equine encephalitis virus
* * * * *
(d) * * *
(3) Any subtypes of Venezuelan equine encephalitis virus except for
Subtypes IAB or IC provided that the individual or entity can verify
that the agent is within the exclusion category.
(e) An attenuated strain of a select agent or an inactive form of a
select toxin may be excluded from the requirements of this part based
upon a determination by the HHS Secretary or Administrator that the
attenuated strain
[[Page 61112]]
or inactivated toxin does not pose a severe threat to public health and
safety, to animal health or to animal products.
(1) To apply for exclusion, an individual or entity must submit a
written request and supporting scientific information. A written
decision granting or denying the request will be issued. An exclusion
will be effective upon notification to the applicant. Exclusions will
be listed on the National Select Agent Registry Web site at http://www.selectagents.gov/.
(2) If an excluded attenuated strain or inactivated toxin is
subjected to any manipulation that restores or enhances its virulence
or toxic activity, the resulting select agent or toxin will be subject
to the requirements of this part.
* * * * *
0
6. Section 73.5 is amended as follows:
0
a. By amending paragraph (a)(3)(i) to remove the words ``Lassa fever
virus'' and ``South American Haemorrhagic Fever viruses (Junin,
Machupo, Sabia, Flexal, Guanarito)'' and by adding, after ``Botulinum
neurotoxins,'' the term ``Botulinum neurotoxin producing species of
Clostridium.''
0
b. By revising paragraph (e) to read as set forth below.
Sec. 73.5 Exemptions for HHS select agents and toxins.
* * * * *
(e) The HHS Secretary may temporarily exempt an individual or
entity from the requirements of this part based on a determination that
the exemption is necessary to provide for the timely participation of
the individual or entity in response to a domestic or foreign public
health emergency. With respect to the emergency involved, the exemption
may not exceed 30 calendar days, except that one extension of an
additional 30 calendar days may be granted.
0
7. Section 73.6 is amended as follows:
0
a. By amending (a)(3)(i) to remove the words ``Brucella melitensis,
Hendra virus, Nipah virus, Rift Valley fever virus, or Venezuelan
equine encephalitis virus'' and adding, after ``Bacillus anthracis'',
the terms ``Burkholderia mallei'' and ``Burkholderia pseudomallei'' in
their place.
0
b. By revising paragraph (e) to read as set forth below.
Sec. 73.6 Exemptions for overlap select agents and toxins.
* * * * *
(e) The HHS Secretary may temporarily exempt an individual or
entity from the requirements of this part based on a determination that
the exemption is necessary to provide for the timely participation of
the individual or entity in response to a domestic or foreign public
health emergency. With respect to the emergency involved, the exemption
may not exceed 30 calendar days, except that one extension of an
additional 30 calendar days may be granted.
* * * * *
0
8. Section 73.9 is amended as follows:
0
a. In paragraph (a)(4), by removing the word ``and.''
0
b. By redesignating paragraph (a)(5) as paragraph (a)(6).
0
c. By adding a new paragraph (a)(5) to read as set forth below.
0
d. By revising the first sentence of paragraph (b) to read as set forth
below.
0
e. In paragraph (c)(1), by removing the words ``Brucella melitensis,''
``Hendra virus,'' ``Lassa fever virus,'' ``Nipah virus,'' ``Rift Valley
fever virus,'' ``South American Haemorrhagic Fever viruses (Junin,
Machupo, Sabia, Flexal, Guanarito),'' and ``Venezuelan equine
encephalitis virus'' and adding, after ``Botulinum neurotoxins,'' the
terms ``Botulinum neurotoxin producing species of Clostridium,
Burkholderia mallei, Burkholderia pseudomallei''.
Sec. 73.9 Responsible Official.
(a) * * *
(5) 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, and
* * * * *
(b) An entity may designate one or more individuals to serve as an
alternate Responsible Official, who acts for the Responsible Official
in his/her absence. * * *
* * * * *
0
9. Section 73.10 is amended as follows:
0
a. By redesignating paragraphs (e) through (j) as paragraphs (f)
through (k) respectively.
0
b. By adding a new paragraph (e) to read as set forth below.
0
c. In newly redesignated paragraph (j), by removing the word ``five''
and adding in its place ``three''.
Sec. 73.10 Restricting access to select agents and toxins; security
risk assessments.
* * * * *
(e) A person with a valid approval from the HHS Secretary or
Administrator to have access to select agents and toxins may request,
through his or her Responsible Official, that the HHS Secretary or
Administrator provide their approved access status to another
registered individual or entity for a specified period of time.
* * * * *
0
10. Section 73.11 is amended as follows:
0
a. By revising paragraph (b) to read as set forth below.
0
b. By revising paragraph (c)(2) to read as set forth below.
0
c. By adding new paragraphs (c)(8), (c)(9), and (c)(10) to read as set
forth below.
0
d. By redesignating paragraphs (e) and (f) as paragraphs (g) and (h),
respectively and by revising newly redesignated paragraph (g) to read
as set forth below.
0
e. By adding new paragraphs (e) and (f) to read as set forth below.
Sec. 73.11 Security.
* * * * *
(b) The security plan must be designed according to a site-specific
risk assessment and must provide graded protection in accordance with
the risk of the select agent or toxin, given its intended use. A
current security plan must be submitted for initial registration,
renewal of registration, or when requested.
(c) * * *
(2) Contain provisions for the control of access to select agents
and toxins, including the safeguarding of animals, including
arthropods, or plants intentionally or accidentally exposed to or
infected with a select agent, against unauthorized access, theft, loss
or release.
* * * * *
(8) Describe procedures for how the Responsible Official will be
informed of suspicious activity that may be criminal in nature and
related to the entity, its personnel, or its select agents or toxins;
and describe procedures for how the entity will notify the appropriate
Federal, State, or local law enforcement agencies of such activity.
(9) Contain provisions for information security that:
(i) Ensure that all external connections to systems which manage
security for the registered space are isolated or have controls that
permit only authorized and authenticated users;
(ii) Ensure that authorized and authenticated users are only
granted access to select agent and toxin related information, files,
equipment (e.g., servers or mass storage devices) and applications as
necessary to fulfill their roles and responsibilities, and that access
is modified when the user's roles and responsibilities change or when
[[Page 61113]]
their access to select agents and toxins is suspended or revoked;
(iii) Ensure that controls are in place that are designed to
prevent malicious code (such as, but not limited to, computer virus,
worms, spyware) from compromising the confidentiality, integrity, or
availability of information systems which manage access to registered
spaces in Sec. 73.11 or records in Sec. 73.17;
(iv) Establish a robust configuration management practice for
information systems to include regular patching and updates made to
operating systems and individual applications; and
(v) Establish procedures that provide backup security measures in
the event that access control systems, surveillance devices, and/or
systems that manage the requirements of section 17 of this part are
rendered inoperable.
(10) Contain provisions and policies for shipping, receiving, and
storage of select agents and toxins, including documented procedures
for receiving, monitoring, and shipping of all select agents and
toxins. These provisions must provide that an entity will properly
secure containers on site and have a written contingency plan for
unexpected shipments.
* * * * *
(e) Entities must conduct complete inventory audits of all affected
select agents and toxins in long-term storage when any of the following
occur:
(1) Upon the physical relocation of a collection or inventory of
select agents or toxins for those select agents or toxins in the
collection or inventory;
(2) Upon the departure or arrival of a principal investigator for
those select agents and toxins under the control of that principal
investigator; or
(3) In the event of a theft or loss of a select agent or toxin, all
select agents and toxins under the control of that principal
investigator.
(f) In addition to the requirements contained in paragraphs (c) and
(d) of this section, the security plan for an individual or entity
possessing a Tier 1 select agent or toxin must also:
(1) Describe procedures for conducting a pre-access suitability
assessment of persons who will have access to a Tier 1 select agent or
toxin;
(2) Describe procedures for how an entity's Responsible Official
will coordinate their efforts with the entity's safety and security
professionals to ensure security of Tier 1 select agents and toxins and
share, as appropriate, relevant information; and
(3) Describe procedures for the ongoing assessment of the
suitability of personnel with access to a Tier 1 select agent or toxin.
The procedures must include:
(i) Self- and peer-reporting of incidents or conditions that could
affect an individual's ability to safely have access to or work with
select agents and toxins, or to safeguard select agents and toxins from
theft, loss, or release;
(ii) The training of employees with access to Tier 1 select agents
and toxins on entity policies and procedures for reporting, evaluation,
and corrective actions concerning the assessment of personnel
suitability; and
(iii) The ongoing suitability monitoring of individuals with access
to Tier 1 select agents and toxins.
(4) Entities with Tier 1 select agents and toxins must prescribe
the following security enhancements:
(i) Procedures that will limit access to a Tier 1 select agent or
toxin to only those individuals who are approved by the HHS Secretary
or Administrator, following a security risk assessment by the Attorney
General, have had an entity-conducted pre-access suitability
assessment, and are subject to the entity's procedures for ongoing
suitability assessment;
(ii) Procedures that limit access to laboratory and storage
facilities outside of normal business hours to only those specifically
approved by the Responsible Official or designee;
(iii) 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;
(iv) A minimum of three security barriers where each security
barrier adds to the delay in reaching secured areas where select agents
and toxins are used or stored. One of the security barriers must be
monitored in such a way as to detect intentional and unintentional
circumventing of established access control measures under all
conditions (day/night, severe weather, etc.) The final barrier must
limit access to the select agent or toxin to personnel approved by the
HHS Secretary or Administrator, following a security risk assessment by
the Attorney General.
(v) All registered space or areas that reasonably afford access to
the registered space must be protected by an intrusion detection system
(IDS) unless physically occupied;
(vi) Personnel monitoring the IDS must be capable of evaluating and
interpreting the alarm and alerting the designated security response
force or law enforcement;
(vii) For powered access control systems, describe procedures to
ensure that security is maintained in the event of the failure of
access control systems due to power disruption affecting registered
space;
(viii) The entity must:
(A) Determine that the response time for security forces or local
police will not exceed 15 minutes or
(B) Provide security barriers that are sufficient to delay
unauthorized access until the response force arrives in order to
safeguard the select agents and toxins from theft, intentional release,
or unauthorized access. The response time is measured from the time of
an intrusion alarm, or report of a security incident, to the arrival of
the responders at the first security barrier.
(5) Entities that possess Variola major virus and Variola minor
virus must have the following additional security requirements:
(i) Require personnel with independent unescorted access to Variola
major or Variola minor virus to have a Top Secret security clearance;
(ii) Require Variola major or Variola minor virus storage locations
to be under the surveillance of closed circuit television that is
monitored;
(iii) After hours access procedures for Variola major or Variola
minor virus must require notification of the entity's security staff
prior to entry into the Variola laboratory and upon exit;
(iv) Require that observation zones be maintained in outdoor areas
adjacent to the physical barrier at the perimeter of the entity and be
large enough to permit observation of the activities of people at that
barrier in the event of its penetration;
(v) Provide for a minimum of four barriers for the protection of
the Variola major or Variola minor virus, one of which must be a
perimeter fence;
(vi) Require a numbered picture badge identification subsystem to
be used for all individuals who are authorized to access Variola major
or Variola minor without escort;
(vii) Require the use, at all times, of properly trained and
equipped security force personnel able to interdict threats identified
in the site specific risk assessment;
(viii) Identify security force personnel designated to strengthen
onsite response capabilities, and that will be onsite and available at
all times to carry out their assigned response duties;
(ix) Provide for security patrols to periodically check external
areas of the registered areas to include physical barriers and building
entrances;
(x) Require that all on-duty security force personnel shall be
capable of
[[Page 61114]]
maintaining continuous communication with support and response assets
by way of security operations center;
(xi) Require that Variola major and Variola minor material in long
term storage be stored in tamper-evident systems;
(xii) Require that all spaces containing working or permanent
Variola major or Variola minor stocks be locked and protected by an
intrusion alarm system that will alarm upon the unauthorized entry of a
person anywhere into the area;
(xiii) Require that alarms required pursuant to this section
annunciate in a continuously manned security operations center located
within the facility; and
(xiv) Require that the security operations center shall be located
within a building so that the interior is not visible from the
perimeter of the protected area.
(g) In developing a security plan, an individual or entity should
consider the document entitled, ``Security Guidance for Select Agent or
Toxin Facilities.'' The document is available on the National Select
Agent Registry Web site at http://www.selectagents.gov/.
* * * * *
0
11. Section 73.12 is amended as follows:
0
a. By revising paragraph (a) to read as set forth below.
0
b. By revising paragraphs (c)(1), (2), and (3) to read as set forth
below.
0
c. By redesignating paragraph (d) as paragraph (e).
0
d. By adding a new paragraph (d) to read as set forth below.
Sec. 73.12 Biosafety.
(a) An individual or entity required to register under this part
must develop and implement a written biosafety plan that is
commensurate with the risk of the select agent or toxin, given its
intended use. The biosafety plan must contain sufficient information
and documentation to describe the biosafety and containment procedures
for the select agent or toxin, including any animals (including
arthropods) or plants intentionally or accidentally exposed to or
infected with a select agent.
* * * * *
(c) * * *
(1) The CDC/NIH publication, ``Biosafety in Microbiological and
Biomedical Laboratories.'' This document is available on the National
Select Agent Registry Web site at http://www.selectagents.gov.
(2) The Occupational Safety and Health Administration (OSHA)
regulations in 29 CFR parts 1910.1200 and 1910.1450. This document is
available on the National Select Agent Registry Web site at http://www.selectagents.gov.
(3) The ``NIH Guidelines for Research Involving Recombinant DNA
Molecules,'' (NIH Guidelines). This document is available on the
National Select Agent Registry Web site at http://www.selectagents.gov.
* * * * *
(d) The biosafety plan must include an occupational health program
for individuals with access to Tier 1 select agents and toxins, and
those individuals must be enrolled in the occupational health program.
* * * * *
0
12. Section 73.13 is amended as follows:
0
a. In paragraph (a), add the phrase ``, or possess products (i.e.,
select agents that are not known to acquire the resistance naturally,
if such acquisition could compromise the control of disease agents in
humans, veterinary medicine, or agriculture, or recombinant and/or
synthetic nucleic acids containing genes for the biosynthesis of select
toxins lethal for vertebrates at an LD[50] < 100 ng/kg body weight)
resulting from,'' after the word ``conduct'' both times it appears.
0
b. By revising paragraph (b) to read as set forth below.
Sec. 73.13 Restricted experiments.
* * * * *
(b) Restricted experiments:
(1) Experiments that involve the deliberate transfer of, or
selection for, a drug resistance trait to select agents that are not
known to acquire the trait naturally, if such acquisition could
compromise the control of disease agents in humans, veterinary
medicine, or agriculture.
(2) Experiments involving the deliberate formation of synthetic or
recombinant nucleic acids containing genes for the biosynthesis of
select toxins lethal for vertebrates at an LD[50] < 100 ng/kg body
weight.
* * * * *
0
13. Section 73.14 is amended as follows:
0
a. By revising paragraph (a) to read as set forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. By redesignating paragraphs (c) and (d) as paragraphs (d) and (f)
respectively.
0
d. By adding a new paragraph (c) to read as set forth below.
0
e. By adding a new paragraph (e) to read as set forth below.
Sec. 73.14 Incident response.
(a) An individual or entity required to register under this part
must develop and implement a written incident response plan based upon
a site specific risk assessment.\2\ The incident response plan must be
coordinated with any entity-wide plans, kept in the workplace, and
available to employees for review.
---------------------------------------------------------------------------
\2\ Nothing in this section is meant to supersede or preempt
incident response requirements imposed by other statutes or
regulations.
---------------------------------------------------------------------------
(b) The incident response plan must fully describe the entity's
response procedures for the theft, loss, or release of a select agent
or toxin; inventory discrepancies; security breaches (including
information systems); severe weather and other natural disasters;
workplace violence; bomb threats and suspicious packages; and
emergencies such as fire, gas leak, explosion, power outage, and other
natural and man-made events.
(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, including any animals (including arthropods) or
plants intentionally or accidentally exposed to or infected with a
select agent.
* * * * *
(e) Entities with Tier 1 select agents and toxins must have the
following additional incident response policies or procedures:
(1) The incident response plan must fully describe the entity's
response procedures for failure of intrusion detection or alarm system;
and
(2) The incident response plan must describe procedures for how the
entity will notify the appropriate Federal, State, or local law
enforcement agencies of suspicious activity that may be criminal in
nature and related to the entity, its personnel, or its select agents
or toxins.
* * * * *
0
14. Section 73.15 is revised to read as follows:
Sec. 73.15 Training.
(a) An individual or entity required to register under this part
must provide information and training on biosafety, security (including
security awareness), and incident response to:
(1) Each individual with access approval from the HHS Secretary or
Administrator before that individual has such access to select agents
and toxins. The training must address the particular needs of the
individual, the work they will do, and the risks posed by the select
agents or toxins; and
[[Page 61115]]
(2) Each individual not approved for access to select agents and
toxins by the HHS Secretary or Administrator before that individual
enters areas where select agents or toxins are handled or stored (e.g.,
laboratories, growth chambers, animal rooms, greenhouses, storage
areas, shipping/receiving areas, production facilities, etc.). Training
for escorted personnel must be based on the risk associated with
accessing areas where select agents and toxins are used and/or stored.
(b) Entities with Tier 1 select agents and toxins must conduct
annual insider threat awareness briefings on how to identify and report
suspicious behaviors.
(c) Refresher training must be provided annually for individuals
with access approval from the HHS Secretary or Administrator or at such
time as the registered individual or entity significantly amends its
security, incident response, or biosafety plans.
(d) The Responsible Official must ensure a record of the training
provided to each individual with access to select agents and toxins and
each escorted individual (e.g., laboratory workers, visitors, etc.) is
maintained. The record must include the name of the individual, the
date of the training, a description of the training provided, and the
means used to verify that the employee understood the training.
0
15. Section 73.16 is amended as follows:
0
a. By redesignating paragraphs (f), (g), (h), and (i) as paragraphs
(i),(j), (k), and (g) respectively.
0
b. In newly redesignated paragraph (g), by removing the words
``packaging and''.
0
c. By adding a new paragraph (f) to read as set forth below.
0
d. By adding a new paragraph (h) to read as set forth below.
0
e. By adding a new paragraph (l) to read as set forth below.
Sec. 73.16 Transfers.
* * * * *
(f) After authorization is provided by APHIS or CDC, the packaging
of the select agent(s) and toxin(s) is performed by an individual
approved by the HHS Secretary or Administrator to have access to select
agents and toxins and is in compliance with all applicable laws
concerning packaging.
* * * * *
(h) Transportation in commerce starts when the select agent(s) or
toxin(s) are packaged for shipment and ready for receipt by a courier
transporting select agent(s) or toxin(s) and ends when the package is
received by the intended recipient who is an individual approved by the
HHS Secretary or Administrator to have access to select agents and
toxins, following a security risk assessment by the Attorney General.
* * * * *
(l) A registered individual or entity transferring an amount of a
HHS toxin otherwise excluded under the provisions of Sec. 73.3(d)
must:
(1) Transfer the amounts only after the transferor uses due
diligence and documents that the recipient has a legitimate need (i.e.,
reasonably justified by a prophylactic, protective, bona fide research,
or other peaceful purpose) to handle or use such toxins.
(2) Report to CDC if they detect a known or suspected violation of
Federal law or become aware of suspicious activity related to a toxin
listed in Sec. 73.3(d) of this part.
0
16. Section 73.17 is amended as follows:
0
a. By revising paragraph (a)(1) introductory text to read as set forth
below.
0
b. By redesignating paragraphs (a)(2) through (a)(6) as paragraphs
(a)(3) through (a)(7) respectively.
0
c. By adding a new paragraph (a)(2) to read as set forth below.
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:
* * * * *
(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);
* * * * *
0
17. Section 73.20 is revised to read as set forth below.
Sec. 73.20 Administrative review.
(a) An individual or entity may appeal a denial, revocation, or
suspension of registration under this part. The appeal must be in
writing, state the factual basis for the appeal, and be submitted to
the HHS Secretary within 30 calendar days of the decision.
(b) An individual may appeal a denial, limitation, or revocation of
access approval under this part. The appeal must be in writing, state
the factual basis for the appeal, and be submitted to the HHS Secretary
within 180 calendar days of the decision.
(c) The HHS Secretary's decision constitutes final agency action.
[FR Doc. 2012-24389 Filed 10-2-12; 11:15 am]
BILLING CODE 4163-18-P