Download:
pdf |
pdfVol. 77
Friday,
No. 194
October 5, 2012
Part III
Department of Health and Human Services
pmangrum on DSK3VPTVN1PROD with RULES3
42 CFR Part 73
Possession, Use, and Transfer of Select Agents and Toxins; Biennial
Review; Final Rule
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
PO 00000
Frm 00001
Fmt 4717
Sfmt 4717
E:\FR\FM\05OCR3.SGM
05OCR3
61084
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
Centers for Disease Control and
Prevention (CDC), Department of Health
and Human Services (HHS).
ACTION: Final rule.
AGENCY:
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 §§ 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.
pmangrum on DSK3VPTVN1PROD with RULES3
SUMMARY:
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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.
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.
ADDRESSES:
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.
The
Preamble to this final rule is organized
as follows:
SUPPLEMENTARY INFORMATION:
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
PO 00000
Frm 00002
Fmt 4701
Sfmt 4700
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 30day 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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
X1CCX2PACGX3X4X5X6CX7, 1
Shigatoxins, Shiga-like ribosome
inactivating proteins, Staphylococcal
Enterotoxins (non-A, non-B, non-C, nonD, and non-E subtypes), and Tick-borne
encephalitis complex viruses (Central
European subtype).
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.
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.
Section No.
Current
Change
73.0 ....................
73.1 ....................
Applicability and related requirements ....
Definitions ................................................
73.2 ....................
73.3 ....................
Purpose and scope .................................
HHS select agents and toxins .................
73.4 ....................
Overlap select agents and toxins ............
73.5 ....................
73.11 ..................
Exemptions for HHS select agents and
toxins.
Exemptions for overlap select agents
and toxins.
Registration and related security risk assessments.
Denial, revocation, or suspension of registration.
Responsible Official .................................
Restricting access to select agents and
toxins; security risk assessments.
Security ....................................................
No change.
Definitions added: Conotoxins; Information security; Occupational exposure; Recombinant nucleic acids; Security barrier; and Synthetic nucleic acids.
No change.
Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the HHS list.
Designates Tier 1 select agents and toxins; adds select agents and toxins; clarifies language; deletes from the overlap list.
Amends the immediate notification list to Tier 1 agents; clarifies language.
73.12 ..................
Biosafety ..................................................
73.6 ....................
73.7 ....................
73.8 ....................
73.9 ....................
73.10 ..................
pmangrum on DSK3VPTVN1PROD with RULES3
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.
61085
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 a-MI and a-GI (shown above) as well
as a-GIA, Ac1.1a, a-CnIA, a-CnIB; X1 = any amino
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
Amends the immediate notification list to Tier 1 agents; clarifies language.
No change.
No change.
Adds new paragraph (a)(5); clarifies language.
Adds new paragraph (e); adds clarifying language.
Revises regulatory text—paragraph (b), (c)(2),(g). Adds new paragraphs (c)(8),
(c)(9), (c)(10), (e), (f).
Revises paragraphs (a) and (c)(1); replaces ‘‘url’’ in paragraph (c)(3); adds new
paragraph (d).
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,
PO 00000
Frm 00003
Fmt 4701
Sfmt 4700
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 DesX.
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61086
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
Section No.
Current
Change
73.13 ..................
73.14 ..................
73.15 ..................
Restricted experiments ............................
Incident response ....................................
Training ....................................................
73.16
73.17
73.18
73.19
73.20
73.21
Transfers .................................................
Records ...................................................
Inspections ..............................................
Notification of theft, loss, or release .......
Administrative review ..............................
Civil money penalties ..............................
Clarifies language.
Revises paragraphs (a), (b); adds new paragraphs (c) and (e).
Revises paragraph (a); redesignates and revises paragraphs (b), (c); adds new
paragraph (b).
Redesignates paragraphs; adds new paragraphs (f), (h), (l).
Revises paragraph (a)(1); adds new paragraph (a)(2).
No changes.
No changes.
Revises paragraphs.
No changes.
..................
..................
..................
..................
..................
..................
A. Modifications to the List of HHS and
Overlap Select Agents and Toxins
HHS 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.
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.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
Addition of Chapare and Lujo Viruses
PO 00000
Frm 00004
Fmt 4701
Sfmt 4700
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)
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
individuals have contracted laboratoryassociated 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 nonlaboratory 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. Positivesense 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 SARSCoV 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
PO 00000
Frm 00005
Fmt 4701
Sfmt 4700
61087
because the virus is not easily
transmitted to humans, the person-toperson 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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61088
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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 = a 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-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 a-conotoxin GI and aconotoxin 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
X1CCX2PACGX3X4X5X6CX7, whereas:
(a) C = Cysteine residues (indicated in bold)
are all present as disulfides, with the 1st
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
and 3rd Cysteine, and the 2nd and 4th
Cysteine forming specific disulfide
bridges;
(b) The consensus sequence includes known
toxins a-MI and a-GI (shown above) as
well as a-GIA, Ac1.1a, a-CnIA, a-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 X1CCX2PACGX3X4X5X6CX7
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
PO 00000
Frm 00006
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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 personto-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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00007
Fmt 4701
Sfmt 4700
61089
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.
E:\FR\FM\05OCR3.SGM
05OCR3
61090
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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.
pmangrum on DSK3VPTVN1PROD with RULES3
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.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 selflimiting 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 longterm 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
PO 00000
Frm 00008
Fmt 4701
Sfmt 4700
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 Shigalike 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 § 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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00009
Fmt 4701
Sfmt 4700
61091
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 noncommunicable 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. Lifethreatening illness occurs only in a few
E:\FR\FM\05OCR3.SGM
05OCR3
61092
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 nonstate 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
PO 00000
Frm 00010
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 welldocumented 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-toperson, 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.
PO 00000
Frm 00011
Fmt 4701
Sfmt 4700
61093
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
(mg) should be designated as Tier 1
toxin, but quantities of less than 500 mg
should not be regulated. One
commenter questioned the ‘‘logic (or
science)’’ behind this decision,
particularly when pharmaceutical
production facilities possessing greater
than 500 mg 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
E:\FR\FM\05OCR3.SGM
05OCR3
61094
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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-byvirus 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00012
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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,
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00013
Fmt 4701
Sfmt 4700
61095
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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61096
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
§ 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00014
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00015
Fmt 4701
Sfmt 4700
61097
located on the campus to ensure day-today 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
E:\FR\FM\05OCR3.SGM
05OCR3
61098
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00016
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 § 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
PO 00000
Frm 00017
Fmt 4701
Sfmt 4700
61099
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 § 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
E:\FR\FM\05OCR3.SGM
05OCR3
61100
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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.
pmangrum on DSK3VPTVN1PROD with RULES3
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 backup 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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:
PO 00000
Frm 00018
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
section of the revised rule, we are
leaving the regulations in their broadlywritten 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.
pmangrum on DSK3VPTVN1PROD with RULES3
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.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 § 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
PO 00000
Frm 00019
Fmt 4701
Sfmt 4700
61101
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.
E:\FR\FM\05OCR3.SGM
05OCR3
61102
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00020
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00021
Fmt 4701
Sfmt 4700
61103
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.
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61104
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00022
Fmt 4701
Sfmt 4700
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
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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.
pmangrum on DSK3VPTVN1PROD with RULES3
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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
Agricultural.Select.Agent.Program@
aphis.usda.gov, 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
PO 00000
Frm 00023
Fmt 4701
Sfmt 4700
61105
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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61106
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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).
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
PO 00000
Frm 00024
Fmt 4701
Sfmt 4700
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/
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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
61107
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 wideranging 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 background
checks.
$240 per person .....................
13,488 approved SRAs;
checks valid for three years.
$432,000 per year 2.
Added Recurring Costs for Affected Entities 3
Submission of Security Plan .............................
Information Security 4
network
connectivity
monitoring
(encryption software).
network connectivity monitoring (firewall
software).
malware software 4 (intrusion detection) ...
malware software (antivirus) .....................
system software updates (dedicated time
for IT Specialist).
$4.95 per submission .............
Estimated 130 annual renewals.
$643.50 per year.
$24–$37 per license ...............
365 registered entities ............
$79–$199 per license .............
365 registered entities ............
$15 per computer ...................
$80 per user per year ............
$2,400 per year ......................
365 registered entities ............
13,488 approved SRAs ..........
365 registered entities ............
$8,760–$13,505 per licensing
period.
$28,835–$72,635 per licensing period.
$5,475 per software update.
$1,079,040 per year.
$876,000 per year.
Total 5 .................................................
approximately $2 million annually, or on average about $5,500 per registered entity.
pmangrum on DSK3VPTVN1PROD with RULES3
Added Costs for Entities that have a Tier 1 Select Agent or Toxin 3,6
Pre-suitability Assessment ................................
Occupational Health Program ..........................
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
$100–$120 per person ...........
$107–$204 per person ...........
PO 00000
Frm 00025
Fmt 4701
13,488 approved SRAs ..........
13,488 approved SRAs ..........
Sfmt 4700
E:\FR\FM\05OCR3.SGM
05OCR3
$1.35–1.62 million.
$1.44–2.75 million.
61108
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
SUMMARY OF THE ESTIMATED MAXIMUM ADDITIONAL COSTS ATTRIBUTABLE TO THE FINAL RULES FOR THE FEDERAL
GOVERNMENT AND AFFECTED ENTITIES 1—Continued
Unit cost
Total 7 .................................................
Number of units
Total additional cost
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 costbenefit 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.
pmangrum on DSK3VPTVN1PROD with RULES3
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
Number of
respondents
Section
Form name
9 CFR 121.5 and 6, 7 CFR 331.5,
43 CFR 73.5 and 6.
§ 121.7, § 331.7, § 73.7 .....................
§ 121.7, § 331.7, § 73.7 .....................
Report of Identification of a Select
Agent or Toxin.
Application for Registration ..............
Amendment to a Certificate of Registration.
Security Plan ....................................
Biosafety/Biocontainment Plan ........
Request Regarding a Restricted Experiment.
Incident Response Plan ...................
Training ............................................
§ 121.11, § 331.11, § 73.11 ...............
§ 121.12, § 331.12, § 73.12 ...............
§ 121.13, § 331.13, § 73.13 ...............
§ 121.14, § 331.14, § 73.14 ...............
§ 121.15, § 331.15, § 73.15 ...............
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
PO 00000
Frm 00026
Fmt 4701
Sfmt 4700
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.)
Number of
responses per
respondent
Average
burden per
response
(in hours)
Total burden
hours
161
3
1
299
7
380
1
7
5
1
35
2,660
380
380
160
1
1
1
5
8
2
1,900
3,040
320
380
380
1
1
5
1
1,900
380
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
Form name
§ 121.16, § 331.16, § 73.16 ...............
Request to Transfer Select Agents
and Toxins.
Records ............................................
Notification of Theft, Loss, or Release.
§ 121.17, § 331.17, § 73.17 ...............
§ 121.19, § 331.19, § 73.19 ...............
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.
pmangrum on DSK3VPTVN1PROD with RULES3
Number of
respondents
Section
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.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
Frm 00027
Fmt 4701
Sfmt 4700
Average
burden per
response
(in hours)
Total burden
hours
290
1
2
580
295
195
1
1
0.5
2
148
390
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 communityacquired 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, Me´nez A,
Letourneux Y, Lancelin JM.
Biochemical Characterization and
Nuclear Magnetic Resonance
Structure of Novel a-Conotoxins
Isolated from the Venom of Conus
consors. Biochemistry. 1999 May
11;38(19):6317–26
PO 00000
Number of
responses per
respondent
61109
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 a -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 BindingCharacteristics 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,
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
61110
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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. Gresı´kova´ M, Kaluzova´ 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 tickborne 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/bio
security/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.national
academies.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.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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
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).
2. Add § 73.0 to read as set forth
below.
■
§ 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.
■ 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.
§ 73.1
Definitions.
*
*
*
*
*
Conotoxins means short, paralytic
alpha conotoxins containing the
following amino acid sequence
X1CCX2PACGX3X4X5X6CX7, 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 a-MI and a-GI (shown above) as
well as a-GIA, Ac1.1a, a-CnIA, a-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;
PO 00000
Frm 00028
Fmt 4701
Sfmt 4700
(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.
*
*
*
*
*
■ 4. Section 73.3 is amended as follows:
■ a. By adding a sentence to the end of
paragraph (a) to read as set forth below.
■ b. By revising paragraph (b) to read as
set forth below.
■ c. In paragraph (c) introductory text,
by adding the phrase ‘‘and/or
Synthetic’’ after the word
‘‘Recombinant’’ each time it appears.
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
d. In paragraph (c)(2) introductory
text, by adding the phrase ‘‘and/or
synthetic’’ after the word
‘‘Recombinant.’’
■ e. By revising paragraph (d)(3) to read
as set forth below.
■ f. By adding a new paragraph (d)(4) to
read as set forth below.
■ g. By adding a new paragraph (d)(5) to
read as set forth below.
■ h. By revising paragraph (e) to read as
set forth below.
■ 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.’’
■
pmangrum on DSK3VPTVN1PROD with RULES3
§ 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
X1CCX2PACGX3X4X5X6CX7)
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 (SARSCoV)
Saxitoxin
South American Haemorrhagic Fever
viruses:
Chapare
Guanarito Junin
Machupo
Sabia
Staphylococcal enterotoxins (subtypes
A–E)
T–2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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 § 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
X1CCX2PACGX3X4X5X6CX7); 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
PO 00000
Frm 00029
Fmt 4701
Sfmt 4700
61111
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.
*
*
*
*
*
■ 5. Section 73.4 is amended as follows:
■ a. By adding a sentence to the end of
paragraph (a) to read as set forth below.
■ b. By revising paragraph (b) to read as
set forth below.
■ c. In paragraph (c) introductory text,
by adding the phrase ‘‘and/or
Synthetic’’ after the word
‘‘Recombinant’’ each time it appears.
■ d. In paragraph (c)(2) introductory
text, by adding the phrase ‘‘and/or
synthetic’’ after the word
‘‘Recombinant.’’
■ e. By adding a new paragraph (d)(3) to
read as set forth below.
■ f. By revising paragraph (e) to read as
set forth below.
■ 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.
§ 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
E:\FR\FM\05OCR3.SGM
05OCR3
61112
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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.
*
*
*
*
*
■ 6. Section 73.5 is amended as follows:
■ 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.’’
■ b. By revising paragraph (e) to read as
set forth below.
§ 73.5 Exemptions for HHS select agents
and toxins.
§ 73.9
Responsible Official.
*
*
*
*
(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.
■ 7. Section 73.6 is amended as follows:
■ 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.
■ b. By revising paragraph (e) to read as
set forth below.
(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.
***
*
*
*
*
*
■ 9. Section 73.10 is amended as
follows:
■ a. By redesignating paragraphs (e)
through (j) as paragraphs (f) through (k)
respectively.
■ b. By adding a new paragraph (e) to
read as set forth below.
■ c. In newly redesignated paragraph (j),
by removing the word ‘‘five’’ and adding
in its place ‘‘three’’.
§ 73.6 Exemptions for overlap select
agents and toxins.
§ 73.10 Restricting access to select agents
and toxins; security risk assessments.
*
*
*
pmangrum on DSK3VPTVN1PROD with RULES3
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.
*
*
*
*
*
■ 8. Section 73.9 is amended as follows:
■ a. In paragraph (a)(4), by removing the
word ‘‘and.’’
■ b. By redesignating paragraph (a)(5) as
paragraph (a)(6).
■ c. By adding a new paragraph (a)(5) to
read as set forth below.
■ d. By revising the first sentence of
paragraph (b) to read as set forth below.
■ 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’’.
*
*
*
*
(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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
*
*
*
*
(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
PO 00000
Frm 00030
Fmt 4701
Sfmt 4700
HHS Secretary or Administrator provide
their approved access status to another
registered individual or entity for a
specified period of time.
*
*
*
*
*
■ 10. Section 73.11 is amended as
follows:
■ a. By revising paragraph (b) to read as
set forth below.
■ b. By revising paragraph (c)(2) to read
as set forth below.
■ c. By adding new paragraphs (c)(8),
(c)(9), and (c)(10) to read as set forth
below.
■ 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.
■ e. By adding new paragraphs (e) and
(f) to read as set forth below.
§ 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
E:\FR\FM\05OCR3.SGM
05OCR3
pmangrum on DSK3VPTVN1PROD with RULES3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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 § 73.11 or records in
§ 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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;
PO 00000
Frm 00031
Fmt 4701
Sfmt 4700
61113
(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
E:\FR\FM\05OCR3.SGM
05OCR3
61114
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
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/.
*
*
*
*
*
■ 11. Section 73.12 is amended as
follows:
■ a. By revising paragraph (a) to read as
set forth below.
■ b. By revising paragraphs (c)(1), (2),
and (3) to read as set forth below.
■ c. By redesignating paragraph (d) as
paragraph (e).
■ d. By adding a new paragraph (d) to
read as set forth below.
pmangrum on DSK3VPTVN1PROD with RULES3
§ 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
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
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.
*
*
*
*
*
■ 12. Section 73.13 is amended as
follows:
■ 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.
■ b. By revising paragraph (b) to read as
set forth below.
§ 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.
*
*
*
*
*
■ 13. Section 73.14 is amended as
follows:
■ a. By revising paragraph (a) to read as
set forth below.
■ b. By revising paragraph (b) to read as
set forth below.
■ c. By redesignating paragraphs (c) and
(d) as paragraphs (d) and (f)
respectively.
■ d. By adding a new paragraph (c) to
read as set forth below.
■ e. By adding a new paragraph (e) to
read as set forth below.
PO 00000
Frm 00032
Fmt 4701
Sfmt 4700
§ 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.
(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.
*
*
*
*
*
■ 14. Section 73.15 is revised to read as
follows:
§ 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
2 Nothing in this section is meant to supersede or
preempt incident response requirements imposed
by other statutes or regulations.
E:\FR\FM\05OCR3.SGM
05OCR3
Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules and Regulations
pmangrum on DSK3VPTVN1PROD with RULES3
(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.
■ 15. Section 73.16 is amended as
follows:
■ a. By redesignating paragraphs (f), (g),
(h), and (i) as paragraphs (i),(j), (k), and
(g) respectively.
■ b. In newly redesignated paragraph
(g), by removing the words ‘‘packaging
and’’.
■ c. By adding a new paragraph (f) to
read as set forth below.
■ d. By adding a new paragraph (h) to
read as set forth below.
VerDate Mar<15>2010
15:29 Oct 04, 2012
Jkt 229001
e. By adding a new paragraph (l) to
read as set forth below.
■
§ 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 § 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
§ 73.3(d) of this part.
16. Section 73.17 is amended as
follows:
■ a. By revising paragraph (a)(1)
introductory text to read as set forth
below.
■
PO 00000
Frm 00033
Fmt 4701
Sfmt 9990
61115
b. By redesignating paragraphs (a)(2)
through (a)(6) as paragraphs (a)(3)
through (a)(7) respectively.
■ c. By adding a new paragraph (a)(2) to
read as set forth below.
■
§ 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 longterm 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);
*
*
*
*
*
■ 17. Section 73.20 is revised to read as
set forth below.
§ 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
E:\FR\FM\05OCR3.SGM
05OCR3
| File Type | application/pdf |
| File Modified | 2012-10-05 |
| File Created | 2012-10-05 |