[Federal Register Volume 77, Number 194 (Friday, October 5, 2012)]
[Rules and Regulations]
[Pages 61083-61115]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-24389]



[[Page 61083]]

Vol. 77

Friday,

No. 194

October 5, 2012

Part III





Department of Health and Human Services





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42 CFR Part 73





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

Federal Register / Vol. 77, No. 194 / Friday, October 5, 2012 / Rules 
and Regulations

[[Page 61084]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Docket No. CDC-2011-0012]

42 CFR Part 73

RIN 0920-AA34


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

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

ACTION: Final rule.

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SUMMARY: In accordance with the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002, the Centers for Disease Control 
and Prevention (CDC) located within the Department of Health and Human 
Services (HHS) has reviewed the list of biological agents and toxins 
that have the potential to pose a severe threat to public health and 
safety and is republishing that list. As a result of our review, we 
have added Chapare virus, Lujo virus, and SARS-associated coronavirus 
(SARS-CoV) to the list of HHS select agents and toxins. We have also 
removed from the list of HHS and overlap select agents and toxins, or 
excluded from compliance with part 73, the agents and toxins described 
in the Executive Summary. Further, in accordance with Executive Order 
13546, ``Optimizing the Security of Biological Select Agents and Toxins 
in the United States,'' HHS/CDC has designated those select agents and 
toxins that present the greatest risk of deliberate misuse with the 
most significant potential for mass casualties or devastating effects 
to the economy, critical infrastructure; or public confidence as ``Tier 
1'' agents; established new security requirements for entities 
possessing Tier 1 agents, including the requirement to conduct pre-
access assessments and on-going monitoring of personnel with access to 
Tier 1 agents and toxins; and made revisions to the regulations to 
clarify regulatory language concerning security, training, biosafety, 
and incident response.
    In a companion document published in this issue of the Federal 
Register, the United States Department of Agriculture (USDA) has made 
parallel regulatory changes.

DATES: Effective Dates: The amendments to Sec. Sec.  73.1, 73.3 through 
73.6, 73.9, 73.10, 73.13, 73.16, 73.17, and 73.20, of Title 42, Code of 
Federal Regulations are effective December 4, 2012. The remaining 
provisions to this final rule are effective April 3, 2013.
    Applicability Dates: By December 4, 2012, all entities that possess 
SARS, Chapare, and Lujo viruses must provide notice to CDC regarding 
their possession of these viruses, and by April 3, 2013, all previously 
unregistered entities must meet all of the requirements of this part.
    The Final Rule timelines are based on the timelines that worked 
effectively for the Federal Select Agent Program Interim Final Rules 
that were published in December 2002. If the regulated community has 
concerns about the established timeline, they can contact Federal 
Select Agent Program for technical assistance.
    Comment Date: Written comments on the new information collection 
contained in this final rule should be received by October 15, 2012.

ADDRESSES: Please send written comments on the new information 
collection contained in this final rule to CDC Desk Officer, Office of 
Management and Budget, Washington, DC 20503 or by fax to (202) 395-
5806.

FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of 
Select Agents and Toxins, Centers for Disease Control and Prevention, 
1600 Clifton Road NE., Mailstop A-46, Atlanta, Georgia 30333. 
Telephone: (404) 718-2000.

SUPPLEMENTARY INFORMATION: The Preamble to this final rule is organized 
as follows:

I. Executive Summary
II. Changes to 42 CFR Part 73
    A. Modifications to the List of HHS and Overlap Select Agents 
and Toxins
    B. Tiering of Select Agents and Toxins
    C. Responses to Other Proposed Changes
    i. Definitions
    ii. Exclusions
    iii. Toxins
    iv. Exemptions
    v. Responsible Official
    vi. Access to Select Agents and Toxins
    vii. Security
    viii. Security for Tier 1 Agents and Toxins
    ix. Biosafety Plan
    x. Restricted Experiments
    xi. Incident Response
    xii. Training
    xiii. Transfers
    xiv. Records
    xv. Administrative Review
    xvi. Guidance Documents
    xvii. Miscellaneous
III. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. Executive Order 12988: Civil Justice Reform
    E. Executive Order 13132: Federalism
    F. Plain Writing Act of 2010
IV. References

I. Executive Summary

    We published an Advance Notice of Proposed Rulemaking (ANPRM) (75 
FR 42363) on July 21, 2010 and a Notice of Proposed Rulemaking (NPRM) 
(76 FR 61206) on October 3, 2011. The NPRM solicited comments regarding 
(1) the appropriateness of the current HHS list of select agents and 
toxins; (2) whether there are other biological agents or toxins that 
should be added to the HHS list; (3) whether biological agents or 
toxins currently on the HHS list should be deleted from the list; (4) 
whether the HHS select agents and toxins list should be tiered based on 
the relative bioterrorism risk of each biological agent or toxin; and 
(5) whether the security requirements for select agents or toxins in 
the highest tier should be further stratified based on type of use or 
other factors. In addition, Executive Order 13546 ``Optimizing the 
Security of Biological Select Agents and Toxins in the United States'' 
directed the HHS Secretary to (1) designate a subset of the select 
agents and toxins list (Tier 1) that presents the greatest risk of 
deliberate misuse with the most significant potential for mass 
casualties or devastating effects to the economy, critical 
infrastructure; or public confidence; (2) explore options for graded 
protection for these Tier 1 agents and toxins to permit tailored risk 
management practices based upon relevant contextual factors; and (3) 
consider reducing the overall number of agents and toxins on the select 
agents and toxins list.
    We provided a 60-day comment period for written comments that ended 
December 2, 2011. We extended the comment period for an additional 30-
day period that ended January 17, 2012.
    The changes to the current regulations include:
    1. Modification of the select agent and toxin list:
    a. The following viruses are added to the HHS select agent list 
based on scientific data related to their significant public health 
risk: SARS-CoV, Lujo and Chapare viruses.
    b. The following agents would no longer be considered HHS select 
agents or toxins, or would be excluded from compliance with part 73: 
Cercopithecine Herpesvirus 1 (Herpes B virus), Clostridium perfringens 
epsilon toxin, Coccidioides posadasii/Coccidioides immitis, Eastern 
Equine Encephalitis virus (South American type only), Flexal virus, 
West African clade of Monkeypox virus, Rickettsia rickettsii, the non-
short, paralytic alpha conotoxins containing the following amino acid 
sequence

[[Page 61085]]

X1CCX2PACGX3X4X5X
6CX7, \1\ Shigatoxins, Shiga-like ribosome 
inactivating proteins, Staphylococcal Enterotoxins (non-A, non-B, non-
C, non-D, and non-E subtypes), and Tick-borne encephalitis complex 
viruses (Central European subtype).
---------------------------------------------------------------------------

    \1\ C = Cysteine residues (indicated in bold) are all present as 
disulfides, with the 1st and 3rd Cysteine, and the 2nd and 4th 
Cysteine forming specific disulfide bridges; The consensus sequence 
includes known toxins [alpha]-MI and [alpha]-GI (shown above) as 
well as [alpha]-GIA, Ac1.1a, [alpha]-CnIA, [alpha]-CnIB; X1 = any 
amino acid(s) or Des-X; X2 = Asparagine or Histidine; P = Proline; A 
= Alanine; G = Glycine; X3 = Arginine or Lysine; X4 = Asparagine, 
Histidine, Lysine, Arginine, Tyrosine, Phenylalanine or Tryptophan; 
X5 = Tyrosine, Phenylalanine, or Tryptophan; X6 = Serine, Threonine, 
Glutamate, Aspartate, Glutamine, or Asparagine; X7 = Any amino 
acid(s) or Des X; and ``Des X'' = ``an amino acid does not have to 
be present at this position.'' For example if a peptide sequence 
were XCCHPA then the related peptide CCHPA would be designated as 
Des-X.
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    c. The following agent would no longer be considered an overlap 
select agent: Venezuelan Equine Encephalitis Virus (subtypes ID and 
IE).
    2. Tiering of the select agent and toxin list:
    a. Tier I agents:

i. HHS select agents and toxins
    (1) Ebola virus
    (2) Francisella tularensis
    (3) Marburg virus
    (4) Variola major virus
    (5) Variola minor virus
    (6) Yersinia pestis
    (7) Botulinum neurotoxin
    (8) Botulinum neurotoxin producing species of Clostridium
ii. Overlap select agents and toxins
    (1) Bacillus anthracis
    (2) Burkholderia mallei
    (3) Burkholderia pseudomallei

    3. Establishing physical security standards for entities possessing 
Tier I select agents and toxins, including the requirement to conduct 
pre-access assessments and on-going monitoring of personnel with access 
to Tier 1 agents and toxins;
    4. Miscellaneous revisions to the regulations to clarify regulatory 
language concerning security, training, biosafety, and incident 
response.
    Costs of the Rule: The entities that will be affected by the final 
rules include research and diagnostic facilities; Federal, State, and 
university laboratories; and private commercial and non-profit 
enterprises. The regulations require registering the possession, use, 
and transfer of select agents or toxins. In addition, the entity is 
required to ensure that the facility where the agent or toxin is housed 
has adequate biosafety and containment measures, that the physical 
security of the premises is adequate, that all individuals with access 
to select agents or toxins have the appropriate education, training, 
and/or experience to handle such agents or toxins, and that complete 
records concerning activities related to the select agents or toxins 
are maintained.
    The final rules will further reduce or minimize the risk of misuse 
of select agents and toxins that have the potential to pose a severe 
threat to human, animal or plant health, or to animal or plant 
products. The USDA/Animal and Plant Health Inspection Service (APHIS) 
and HHS/CDC recognize that several of the required measures of the 
regulations may impose certain operational costs upon affected 
entities, particularly entities that have the newly designated Tier 1 
select agents and toxins. In many cases, however, the affected entities 
already employ some or all of the required measures. Compliance costs 
actually incurred will therefore vary from one entity to the next.
    While information on the specific changes that would need to occur 
at individual sites and the associated costs was not readily available 
during proposed rulemaking, some general observations regarding the 
potential costs were presented. These general cost observations can be 
found in table 2 in the Regulatory Impact Analysis located at: 
www.regulations.gov and at http://www.selectagents.gov/.
    Benefits of the Rule: The objectives of the final rules are to 
create a means of ensuring enhanced oversight in the transfer, storage, 
and use of select agents and toxins; define the security procedures and 
suitability assessments for pre-access suitability and continual 
monitoring of individuals with access to Tier 1 select agents and 
toxins; and require that entities in possession of such agents and 
toxins develop and implement effective means of biosafety, information 
security, and physical security. The overall benefit of the amended 
provisions will be a reduced likelihood of the accidental or 
intentional release of a select agent or toxin and the avoidance of 
costs associated with such a release. The goal of the amended 
regulations is to enhance the protection of human, animal, and plant 
health and safety.

II. Changes to 42 CFR Part 73

    The table below describes the changes to the current regulation.

------------------------------------------------------------------------
       Section No.               Current                 Change
------------------------------------------------------------------------
73.0.....................  Applicability and    No change.
                            related
                            requirements.
73.1.....................  Definitions........  Definitions added:
                                                 Conotoxins; Information
                                                 security; Occupational
                                                 exposure; Recombinant
                                                 nucleic acids; Security
                                                 barrier; and Synthetic
                                                 nucleic acids.
73.2.....................  Purpose and scope..  No change.
73.3.....................  HHS select agents    Designates Tier 1 select
                            and toxins.          agents and toxins; adds
                                                 select agents and
                                                 toxins; clarifies
                                                 language; deletes from
                                                 the HHS list.
73.4.....................  Overlap select       Designates Tier 1 select
                            agents and toxins.   agents and toxins; adds
                                                 select agents and
                                                 toxins; clarifies
                                                 language; deletes from
                                                 the overlap list.
73.5.....................  Exemptions for HHS   Amends the immediate
                            select agents and    notification list to
                            toxins.              Tier 1 agents;
                                                 clarifies language.
73.6.....................  Exemptions for       Amends the immediate
                            overlap select       notification list to
                            agents and toxins.   Tier 1 agents;
                                                 clarifies language.
73.7.....................  Registration and     No change.
                            related security
                            risk assessments.
73.8.....................  Denial, revocation,  No change.
                            or suspension of
                            registration.
73.9.....................  Responsible          Adds new paragraph
                            Official.            (a)(5); clarifies
                                                 language.
73.10....................  Restricting access   Adds new paragraph (e);
                            to select agents     adds clarifying
                            and toxins;          language.
                            security risk
                            assessments.
73.11....................  Security...........  Revises regulatory text--
                                                 paragraph (b),
                                                 (c)(2),(g). Adds new
                                                 paragraphs (c)(8),
                                                 (c)(9), (c)(10), (e),
                                                 (f).
73.12....................  Biosafety..........  Revises paragraphs (a)
                                                 and (c)(1); replaces
                                                 ``url'' in paragraph
                                                 (c)(3); adds new
                                                 paragraph (d).

[[Page 61086]]

 
73.13....................  Restricted           Clarifies language.
                            experiments.
73.14....................  Incident response..  Revises paragraphs (a),
                                                 (b); adds new
                                                 paragraphs (c) and (e).
73.15....................  Training...........  Revises paragraph (a);
                                                 redesignates and
                                                 revises paragraphs (b),
                                                 (c); adds new paragraph
                                                 (b).
73.16....................  Transfers..........  Redesignates paragraphs;
                                                 adds new paragraphs
                                                 (f), (h), (l).
73.17....................  Records............  Revises paragraph
                                                 (a)(1); adds new
                                                 paragraph (a)(2).
73.18....................  Inspections........  No changes.
73.19....................  Notification of      No changes.
                            theft, loss, or
                            release.
73.20....................  Administrative       Revises paragraphs.
                            review.
73.21....................  Civil money          No changes.
                            penalties.
------------------------------------------------------------------------

A. Modifications to the List of HHS and Overlap Select Agents and 
Toxins

    The changes to the list of HHS select agents and toxins are based 
on comments received in response to the NPRM, recommendations from the 
Federal Experts Security Advisory Panel (FESAP) and HHS/CDC's 
Intragovernmental Select Agents and Toxins Technical Advisory Committee 
(ISATTAC), and our review of current scientific literature.
    Executive Order 13546 established the FESAP to advise the HHS 
Secretary on the designation of Tier 1 agents and toxins, the reduction 
in the number of agents on the select agent list, the establishment of 
appropriate practices to ensure reliability of personnel with access to 
Tier 1 agents, and the establishment of the appropriate practices for 
physical security and cyber security for facilities that possess Tier 1 
agents.
    The ISATTAC was established by the CDC Director and is comprised of 
Federal government employees from the CDC, the National Institutes of 
Health (NIH), the Food and Drug Administration (FDA), the Biomedical 
Advanced Research and Development Authority (BARDA) within the HHS 
Office of the Assistant Secretary for Preparedness and Response (HHS/
ASPR), the USDA/APHIS, USDA/Agricultural Research Service (ARS), USDA/
CVB (Center for Veterinary Biologics), the Department of Homeland 
Security (DHS), and the Department of Defense (DOD). The purpose of the 
ISATTAC is to assist CDC's Division of Select Agents and Toxins in 
performing its regulatory functions under the select agent regulations, 
including conducting a review of the select agents and toxins list.
    We received 113 comments that addressed the composition of the 
select agents and toxins list.
    As discussed below, the final rule removes or excludes 13 select 
agents and toxins, added 3 select agents, and designated 11 select 
agents and toxins as ``Tier 1'' agents.
HHS Select Agents and Toxins
Addition of Chapare and Lujo Viruses
    On August 19, 2009, we proposed adding the haemorrhagic fever virus 
Chapare, to the list of select agents (74 FR 41829). Chapare virus is a 
recently described New World arenavirus that is associated with fatal 
hemorrhagic fever syndrome and is most closely related to Sabia virus, 
an HHS select agent (Ref 1).
    On October 3, 2011, we proposed adding the haemorrhagic fever virus 
Lujo to the list of select agents (76 FR 61206). According to available 
reports, Lujo virus (1) caused a fatal outbreak of hemorrhagic fever, 
(2) has a case fatality rate of 80 percent, (3) has been 
phylogenetically identified as an arenavirus, and (4) is related to 
those members of the Old World arenaviridae family (Junin, Machupo, 
Sabia, Guanarito, and Lassa) listed as HHS select agents that cause 
hemorrhagic fever and pose a significant risk to public health and 
safety (Ref 2).
    Some commenters argued that there does not appear to be valid 
evidence that these viruses could be effectively utilized as terrorism 
agents. Another commenter recommended that all hemorrhagic arenaviruses 
be included in the select agent list.
    We made no changes to the HHS list of select agents and toxins 
based on these comments. Although the literature on these newly 
described viruses is small and recent, both viruses have thus far 
produced high morbidity and mortality rates. Both Lujo and Chapare 
virus share other characteristics with regulated hemorrhagic fever 
viruses (Junin, Machupo, Sabia, Guanarito, and Lassa). As a taxonomic 
group, the hemorrhagic arenaviruses exhibit distinct differences in 
morbidity, mortality, transmissibility, and degree of pathogenicity. 
Therefore our consideration of whether to add a particular arenavirus 
to the list is made on a taxon-by-taxon basis. As more information 
becomes known about the public health risks of these two new 
hemorrhagic fever viruses, their status as select agents can be 
reassessed.
    Individuals and entities that currently possess Chapare or Lujo 
virus, if they are not already registered entities, will have to either 
transfer the organism or genomic material to a registered entity, 
destroy their stocks and report the destruction to HHS/CDC, or if they 
choose to retain their stocks, register with HHS/CDC and comply with 
all applicable regulations as provided in this final rule. We also 
recognize that those entities that choose to become registered will 
need time to come into full compliance with the requirements of the 
regulations. This final rule will become effective on December 4, 2012. 
On and after that date, any individual or entity possessing, using, or 
transferring any listed select agent or toxin must be in compliance 
with the provisions of each part. However, to minimize the disruption 
of critical research or educational projects involving Chapare or Lujo 
virus that are underway as of the effective date of these regulations, 
we are providing that any individual or entity possessing Chapare or 
Lujo virus as of the effective date (current possessors) will be 
afforded additional time to reach full compliance with the regulations 
in each part. Accordingly, by December 4, 2012, all entities that 
possess Chapare and/or Lujo virus must provide notice to HHS/CDC 
regarding their possession of Chapare and/or Lujo virus, and by April 
3, 2013, all previously unregistered entities must meet all of the 
requirements of this part.
Addition of SARS-Associated Coronavirus (SARS-CoV)
    SARS-CoV is associated with one of the most significant pandemics 
of the 21st century. According to the World Health Organization, the 
2002-2003 SARS pandemic involved 29 countries, produced over 8000 cases 
of disease, and resulted in 774 deaths (Ref 3). Since the end of the 
pandemic the majority of reported SARS-CoV infections have occurred in 
laboratorians, or individuals who had close contact with infected 
laboratorians (Ref 4-6). At least 13 (6 primary cases and 7 contacts)

[[Page 61087]]

individuals have contracted laboratory-associated SARS-CoV infections 
(Ref 7).
    On July 13, 2009, we proposed the addition of SARS-CoV to the list 
of select agents and toxins (74 FR 33401). We received ten comments 
from representatives of universities, public health laboratories, 
commercial, and government facilities, all arguing that SARS-CoV should 
not be added to the select agent list. Commenters believed that further 
deliberation of the biosafety and biosecurity issues involved with this 
agent should be considered due to the implications for research and 
public health activities. The commenters further reasoned that adding 
SARS-CoV as a select agent would decrease public safety and security by 
preventing expert researchers from pursuing important work due to what 
they described as the additional costs and onerous burdens inherent 
with the select agent registration and compliance process.
    During the public comment period for this rulemaking we received 
three comments from representatives from universities and a public 
health laboratory that recommended the addition of SARS-CoV to the list 
of select agents and toxins because (1) it exhibited high 
transmissibility and high lethality; (2) caused epidemics on four 
continents with significant mortality; (3) had a major economic impact; 
and (4) had a major psychological impact. Commenters further argued 
that the virus has demonstrated its ability to cause a contagious 
disease, has caused several laboratory infections (including one 
incident that led to cases in non-laboratory contacts) and is a virus 
which no longer circulates in nature.
    We agree with the commenters who supported the addition of SARS-CoV 
to the list of select agents and toxins because of the significant 
impact of SARS-CoV on the public health system, the high degree of 
pathogenicity, and the lack of vaccines or proven therapeutics 
currently available to prevent or treat SARS-CoV infections. 
Additionally, we note that the virus no longer appears to be naturally 
circulating in humans, raising the concern that the general population 
does not possess a significant level of immunity.
    The genome of SARS-CoV will be regulated as an HHS select agent. As 
a member of the Coronarviridae family, SARS-CoV is an enveloped virus 
with a positive-sense RNA genome. Positive-sense RNA viruses that 
utilize host polymerases contain nucleic acids, in and of themselves, 
that can produce infectious forms of the virus. The select agent 
regulations apply to nucleic acids that can produce infectious forms of 
any of the select agent viruses (See section 3(c) of 42 CFR part 73, 9 
CFR part 121, and 7 CFR part 331).
    Based on information received from the HHS/CDC's Etiologic Agent 
Import Permit Program and the HHS/CDC's Office of Infectious Diseases, 
there are 119 entities that currently possess SARS-CoV. Of those 119 
entities, 77 entities are registered with the Federal Select Agent 
Program; 42 entities are not registered. Of the 42 non-registered 
entities, only 38 may possess SARS-CoV or SARS-CoV genomic material 
(RNA). The 38 non-registered entities that may possess SARS-CoV or 
SARS-CoV genomic material (RNA) include 10 academic, 22 commercial, 5 
State government, and 1 Federal government institutions.
    Entities and individuals that currently possess SARS-CoV or SARS-
CoV genomic material (RNA) will have to either (1) transfer the 
organism or genomic material to a registered entity; (2) destroy their 
stocks and report the destruction to CDC; or (3) register with HHS/CDC 
or USDA/APHIS to possess SARS-CoV and comply with all applicable 
regulations as provided in this final rule. We also recognize that 
those entities that choose to become registered with the Federal Select 
Agent Program will need time to come into full compliance with the 
requirements of the regulations. Since this final rule will become 
effective on December 4, 2012 and any individual or entity possessing, 
using, or transferring any listed agent or toxin must be in compliance 
with the provisions of each part on or after that date, we are 
providing that any individual or entity possessing SARS-CoV as of the 
effective date (current possessors) will be afforded additional time to 
reach full compliance with the regulations in each part. Accordingly, 
by December 4, 2012, all entities that possess SARS-CoV must provide 
notice to HHS/CDC regarding their possession of SARS-CoV, and by April 
3, 2013, all previously unregistered entities must meet all of the 
requirements of this part. We are extending the effective date for 
these currently non-registered entities to minimize the disruption of 
critical research or educational projects involving SARS-CoV that are 
underway as of the effective date of these regulations.
Removal of Cercopithecine Herpesvirus 1 (Herpes B Virus)
    We are removing Cercopithecine herpesvirus 1 (Herpes B virus) from 
the HHS list of select agents and toxins. We proposed the removal of 
Cercopithecine herpesvirus 1 (Herpes B virus) from the HHS list of 
select agents and toxins because the virus is not easily transmitted to 
humans, the person-to-person transmission risk is small, the numbers of 
recorded human infections are low, and multiple licensed antiviral 
treatments for Herpes B infections are available. The only comments 
that we received on this proposal were supportive for the removal.
Removal of Clostridium Perfringens Epsilon Toxin
    The proposed rule retained C. perfringens epsilon toxin on the list 
of select agents and toxins. The final rule removes it. Commenters 
questioned why C. perfringens epsilon toxin was listed as a select 
agent since its production is licensed by USDA under the Virus-Serum-
Toxin Act. In addition, commenters argued that from a veterinary 
laboratory perspective, C. perfringens epsilon toxin is commonly 
detected in the gastrointestinal tract during routine post-mortem 
diagnostic testing and the quantity of toxin recovered from a positive 
diagnostic sample would be far below the 100 mg exclusion amount 
provided for in the select agent regulations. Commenters also supplied 
scientific data in support of removal of C. perfringens epsilon toxin 
from the select agent and toxin list (Ref 8).
    Although many of the concerns raised by the commenters are 
addressed by the exemption and exclusion provisions in the regulations 
(42 CFR 73.3 and 73.5), we agree with commenters and have determined 
that C. perfringens epsilon toxin should be removed from the list of 
HHS select agents and toxins. C. perfringens epsilon toxin was 
originally included on the select agent list because of its relatively 
low (LD)50 (lethal dose fifty: the amount of the toxin 
required to kill 50 percent of the test population) in rodents and 
moderate toxicity when in aerosol form. The LD50 results for 
C. perfringens epsilon toxin are based on a mouse in vivo injection 
model, which does not completely mimic a natural infection, and 
therefore may not accurately represent the human LD50. 
Additional significant factors in our determination to remove C. 
perfringens epsilon toxin include the absence of known human cases of 
disease, a lack of human or non-human primate toxicity data, and 
insufficient new data to indicate that C. perfringens epsilon toxin is 
a significant threat to public health and safety.
Reduction of Conotoxins on the HHS List of Select Agents and Toxins
    The term ``conotoxin'' is used broadly to comprise a very large 
number of polypeptides isolated from the venom of

[[Page 61088]]

fish-hunting marine snails of the Conus genus of gastropod mollusks. 
Many of these molecules are neurologically active in mammals. Although 
we did not propose the removal for conotoxins, we did receive multiple 
comments that conotoxins should be removed from the list of select 
agents and toxins for the following reasons:
     Commenters noted that most components isolated from cone 
snail venom are harmless to humans; in fact, one of them (MVIIA = 
Ziconotide = PrialtTM) is an FDA-approved commercial drug 
for the treatment of chronic pain. Several other conopeptides have 
reached clinical trials at various levels (CVID, Conantokin-G, 
Contulakin-G, Xe2174 and ACV1 = [alpha] conotoxin Vc1.1), and they all 
show extremely low levels of toxicity to humans.
     Commenters pointed to the fact that the term ``conotoxin'' 
can be applied to several hundred thousand compounds found in Conus 
venoms that are not toxic at all to humans is evidence that this 
designation needs to be revised. Furthermore, the designation of 
``conotoxins'' as select toxins imposes an enormous and unnecessary 
burden for the development of cone snail-based therapeutics.
    Other comments included the following:
     Conotoxins have never been weaponized.
     Conotoxins must be delivered parenterally.
     Conotoxins are difficult to manufacture.
     Conotoxins are not self[hyphen]replicating.
    We agree, in part, with the commenters. Based upon available 
experimental evidence, most known conotoxins (i.e., ``conopeptides'') 
do not possess sufficient acute toxicity to pose a significant public 
health threat, and many are employed as useful research tools or 
potential human therapeutics. However, currently available data 
demonstrate that the sub-class of conotoxins generally called ``short, 
paralytic alpha conotoxins,'' exemplified by [alpha]-conotoxin GI and 
[alpha]-conotoxin MI do possess sufficient acute toxicity by multiple 
routes of exposure, biophysical stability, ease of synthesis, and 
availability. Therefore, we have modified the type of conotoxins that 
are regulated to focus on those that pose a threat to public health and 
safety. The conotoxins that remain on the HHS list will be limited to 
the short, paralytic alpha conotoxins containing the following amino 
acid sequence 
X1CCX2PACGX3X4X5X
6CX7, whereas:

(a) C = Cysteine residues (indicated in bold) are all present as 
disulfides, with the 1st and 3rd Cysteine, and the 2nd and 4th 
Cysteine forming specific disulfide bridges;
(b) The consensus sequence includes known toxins [alpha]-MI and 
[alpha]-GI (shown above) as well as [alpha]-GIA, Ac1.1a, [alpha]-
CnIA, [alpha]-CnIB
(c) X1 = any amino acid(s) or Des-X;
(d) X2 = Asparagine or Histidine;
(e) P = Proline;
(f) A = Alanine;
(g) G = Glycine;
(h) X3 = Arginine or Lysine;
(i) X4 = Asparagine, Histidine, Lysine, Arginine, 
Tyrosine, Phenylalanine or Tryptophan;
(j) X5 = Tyrosine, Phenylalanine, or Tryptophan;
(k) X6 = Serine, Threonine, Glutamate, Aspartate, 
Glutamine, or Asparagine;
(l) X7 = Any amino acid(s) or Des X; and
(m) ``Des X'' = ``an amino acid does not have to be present at this 
position.'' For example if a peptide sequence were XCCHPA then the 
related peptide CCHPA would be designated as Des-X.

    The short, paralytic alpha conotoxins containing the following 
amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7 will be considered a select toxin if the 
total amount (all forms) under the control of a principal investigator, 
treating physician or veterinarian, or commercial manufacturer or 
distributor exceeds 100 mg at any time (Ref 9-13). As such, we have 
added the definition of regulated conotoxins.
Removal of Coccidioides Posadasii/Coccidioides Immitis
    We are removing C. posadasii/C. immitis from the HHS list of select 
agents and toxins. We proposed the removal of C. posadasii/C. immitis 
based on the availability of licensed treatments for Coccidioides 
infection and a lowering of our assessment of the impact of 
Coccidioides infection on human health, as indicated by the high 
proportion of subclinical cases observed in endemic areas (Ref 14). The 
only comments that we received on this issue were supportive of the 
removal of C. posadasii/C. immitis from the HHS list of select agents 
and toxins.
Removal of Flexal Virus
    We are removing Flexal virus from the HHS list of select agents and 
toxins. We proposed the removal of Flexal virus based on the lack of 
severity of disease and the lack of significant outbreaks of disease 
associated with this virus in humans. The only comments that we 
received on this issue were supportive of the removal of Flexal virus 
from the HHS list of select agents and toxins.
Removal of the West African Clade of Monkeypox Virus
    We are excluding the West African clade of Monkeypox from 
regulation under this part, while retaining the Congo Basin clade of 
Monkeypox. We proposed the retention of Monkeypox on the list of select 
agents and toxins, but invited comments on removing the West African 
clade of Monkeypox virus from the list. Monkeypox is closely related to 
smallpox virus and produces a clinical syndrome similar to that seen 
with smallpox. Mortality rates associated with Monkeypox infections 
have been reported to be as high as 17 percent (Ref 15-16). Monkeypox 
can be separated into two genetically distinct variants called the West 
African and Congo Basin clades. Clinical and laboratory studies 
indicate that the Congo Basin clade is significantly more pathogenic to 
humans and animals than the West African clade (Ref 17-18). The 37 
confirmed cases of human Monkeypox associated with the 2003 importation 
of a West African strain from Ghana into the United States were 
associated with no case-fatalities and no observed chain of human-to-
human transmission. Clinically severe human disease associated with 
West African strains is rare and this virus clade has not been 
associated with human mortality (Ref 19). Based on this information, we 
are excluding the West African clade from regulation under this part, 
while retaining the Congo Basin clade.
    One commenter disagreed with the proposed retention of Monkeypox 
virus, regardless of clade, as a select agent. We agreed in part with 
the commenter. As indicated above, we recognize that significant 
differences in pathogenicity exist between the West African and Congo 
Basin clades and have determined that viruses of only the Congo Basin 
clade merit regulation as HHS select agents. We also note that there 
are published diagnostic tests that differentiate Congo Basin from West 
African clades (Ref 19).
    While the listing found in section 3 (HHS select agents and toxins) 
will continue to read ``Monkeypox'', a new subparagraph (d)(5) in that 
same section, excludes from regulation any West African clade of the 
Monkeypox virus provided that an individual or entity can verify that 
the Monkeypox virus is the West African clade.
Removal of South American Genotypes of Eastern Equine Encephalitis 
Virus (EEEV)
    We proposed the removal of South America EEEV genotypes from the 
list of HHS select agents and toxins and the final rule is consistent 
with the proposed rule.
    One commenter believed that all strains of EEEV should be removed 
from

[[Page 61089]]

the select agent list for the following reasons:
     The commenter noted that EEEV is endemic in Florida, but 
does not cause human epidemics even with high prevalence in the 
ecosystem and evidence of natural transmission activity to sentinels.
     The commenter noted that person-to-person transmission 
does not occur; transmission is only through mosquito bite. An average 
of only 5 human cases are identified annually in the United States.
     The commenter noted that there is a vaccine available for 
horses that can prevent disease even if there is ongoing natural virus 
transmission.
     The commenter noted that states with high endemicity of 
EEEV often have a state public health laboratory proactive 
comprehensive arbovirus surveillance program to define risk of human 
infection. Serum-neutralization assays are an essential part of such a 
program and require live virus which is needed for test performance. 
This work is performed at BSL3 level and additional federal regulatory 
requirements do not add to the safety of handling or storing the virus.
     The commenter noted that genotype analysis to determine if 
an EEEV strain is a North American or South American genotype is not 
practical in a state public health laboratory, where the goal is 
surveillance, not research.
     The commenter noted that this agent is not stable in the 
environment outside of its natural host (mosquitoes, birds).
    We made no changes to the list of HHS select agents and toxins 
based on this comment. North American EEEV (NA EEEV), genotype strains, 
which are the strains responsible for human and equine disease, are all 
genetically very similar to each other (less than 3 percent divergence 
at the nucleotide level) and can be easily distinguished from South 
American EEEV (SA EEEV) genotype strains by sequencing. NA EEEV 
genotype strains differ from SA EEEV by greater than 20 percent at the 
nucleotide level and approximately 10 percent at the amino acid level. 
We are aware that EEEV is endemic in Florida, that person-to-person 
transmission does not occur, that an equine vaccine is available, and 
that EEEV isn't stable outside of its natural host. Among the factors 
that we considered in retaining the NA EEEV genotype were that this 
genotype exhibits high morbidity, high mortality, and has the potential 
to be weaponized. We also appreciate that public health laboratories 
focus on surveillance and utilize assays that do not specifically 
determine which subtype of EEEV is present. However, we believe that 
the risks posed by the NA EEEV outweigh the practical issues associated 
with subtype determination. Because the NA EEEV genotype strains are 
distinctly different from SA EEEV in their genetics, epidemiology, and 
pathogenicity, we believe that the two genotypes can be distinguished 
from each other in the laboratory.
    While the listing found in section 3 (HHS select agents and toxins) 
will continue to read ``Eastern Equine Encephalitis virus,'' a new 
subparagraph (d) (5) in that same section excludes from regulation, any 
South American genotypes of Eastern Equine Encephalitis virus provided 
that an individual or entity can verify that the Eastern Equine 
Encephalitis virus is one of the South American genotypes.

Rickettsia prowazekii and Rickettsia rickettsii

    The proposed rule retained R. rickettsii and R. prowazekii on the 
HHS list of select agents and toxins. The final rule removes R. 
rickettsii and retains R. prowazekii.
    Commenters argued that R. rickettsii and R. prowazekii should be 
removed from the select agent list based on:
     The same rationale used by HHS/CDC to propose removal of 
Herpes B virus from the HHS select agent list;
     R. rickettsii and R. prowazekii are readily available in 
nature, and can be isolated from natural sources such as ticks and 
flying squirrel lice;
     R. rickettsii and R. prowazekii are not contagious;
     Human infections due to these agents are capable of being 
treated with doxycycline, other tetracyclines, and chloramphenicol;
     The bacteria are fastidious obligate intracellular 
pathogens, thus propagation requires growth in cultured host cells; and
     The inclusion of these rickettsiae on the HHS select agent 
list will produce no significant improvements in safety for the 
American public.
    After careful consideration of these comments, we agree with the 
commenters that R. rickettsii should be removed from the HHS list of 
select agents and toxins. Significant factors in our reconsideration 
include the poor environmental stability of this species, the lack of 
person-to-person transmission especially in the absence of an 
appropriate vector, the availability of effective antibiotic 
treatments, and the difficulty in growing and purifying substantial 
quantities of these agents in vitro. However, we have determined that 
R. prowazekii should be retained as a select agent. This species was 
investigated as a potential weapon by multiple national offensive 
programs prior to the Biological Weapons Convention, and has many 
characteristics of a bioweapon. The infectious dose for R. prowazekii 
is unknown but has been estimated to be as little as 10 organisms (Ref 
20). There are currently no licensed vaccines against R. prowazekii 
available for human use in the United States. Until additional studies 
can be completed to better understand the potential risk of an 
intentional release of this organism to the public, we have determined 
to retain R. prowazekii on the HHS Select Agent List.
Removal of Shigatoxins and Shiga-Like Ribosome Inactivating Proteins
    We proposed the retention of Shigatoxins and Shiga-like ribosome 
inactivating proteins on the HHS list of select agents and toxins. One 
commenter asked us to reconsider the retention of Shigatoxins and 
Shiga-like ribosome inactivating proteins as a select toxin based on 
the following criteria:
     Introduction of Shigatoxins by the aerosol route has not 
been reported;
     Shigatoxins are extremely difficult to synthesize in 
quantities that are toxic to humans;
     Expression of toxin in bacteria is self-limiting due to 
inhibitory effects on bacterial cells of over-expressed toxin; and
     There are limitations to purification and concentration of 
Shigatoxins that make them impractical and ill-suited to methods of 
dispersal that would require large quantities of toxin for delivery by 
food, water, or air.
    We have considered all of the points raised by the commenter and, 
after additional consultations with subject matter experts, agree that 
compelling data exist to support the removal of Shigatoxin and Shiga-
like ribosome inactivating proteins from the HHS list of select agents 
and toxins. Therefore, we have decided to remove Shigatoxin and Shiga-
like ribosome inactivating proteins from the HHS list of select agents 
and toxins. Additional significant factors considered in our 
determination include the difficulty in producing or administering 
large quantities of toxin via the aerosol route, their poor 
environmental stability, the lack of significant toxicity seen with 
oral exposure (which is the route by which an individual becomes 
intoxicated by Shigatoxin), and the observation that the worst effects 
seen with intoxication are associated with other pathogenic factors 
from the Shigatoxin-producing strains of E. coli, which are not 
regulated.

[[Page 61090]]

Reduction of Staphylococcal Enterotoxins on the HHS List of Select 
Agents and Toxins
    We proposed the reduction of Staphylococcal Enterotoxins on the HHS 
list of select agents and toxins to only include Staphylococcal 
Enterotoxins A, B, C, D, and E. Commenters were concerned that the 
``incredible simplicity'' of obtaining Staphylococcal species from 
environmental sources and screening them for the presence of 
enterotoxins ``utterly neuters'' the intent of the select agent 
regulations to provide security against the misuse of such agents. A 
commenter requested ``CDC to consider alternative regulatory strategies 
to balance the need of legitimate scientific access to such agents so 
that it is not harder to use them than for a terrorist.''
    We made no changes to the HHS list of select agents and toxins 
based on this comment. Current data based on emesis in non-human 
primates demonstrates that Staphylococcal Enterotoxins A, B, C, D, and 
E pose a significant threat to public health and safety. In addition, 
we note that these enterotoxins exhibit significant environmental 
stability, which contributes to their public health risk. It should be 
noted that this revision represents a significant reduction of the 
types of Staphylococcal enterotoxins regulated as HHS select toxins.
Reorganization of Tick-Borne Encephalitis Complex Viruses (TBEV)
    We proposed the removal of TBEV Central European subtype from the 
HHS list of select agents and toxins because the TBEV Central European 
Tick-borne subtype has been shown to be less virulent in humans than 
the Far Eastern subtype (Ref 21). We also proposed to reorganize the 
listing of the TBEV to reflect the current nomenclature given by the 
International Committee on Taxonomy of Viruses. For TBEV proper, there 
are now just three recognized subtypes: Central European, Far Eastern, 
and Siberian. The Russian Spring and Summer Encephalitis designation is 
no longer recognized (Ref 22). Two other viruses on the HHS list of 
select agents and toxins, Kyasanur Forest Disease virus and Omsk 
Hemorrhagic Fever virus, are no longer classified as TBEV. In 
recognition of these taxonomic changes, we proposed to include these 
viruses on the HHS list of select agents and toxins as follows:

Tick-borne encephalitis virus
Far Eastern subtype
Siberian subtype
Kyasanur Forest disease virus
Omsk Hemorrhagic fever virus.

All comments that we received on this issue were supportive of the 
removal of TBEV Central European subtype from the HHS list of select 
agents and toxins and the reorganization of the listing of the TBEV to 
reflect the current nomenclature.
Retention of Coxiella burnetii
    We proposed the retention of C. burnetii on the HHS list of select 
agents and toxins. Commenters argued that this agent should be removed 
because:
     This organism is ubiquitous in the United States, and can 
be detected in greater than 90 percent of bulk milk tank samples. 
Despite this, significant human consequences to infection with this 
agent are rare.
     The organism is readily susceptible to available 
antibiotics.
    While perhaps easily transmitted to humans, the disease caused by 
this organism is generally mild and self-limiting in humans and does 
not have a huge economic impact in animals. It therefore does not have 
the potential to be an effective terrorist weapon. We made no changes 
to the HHS list of select agents and toxins based on these comments. We 
recognize that there is a low level of mortality associated with this 
agent; that it is present in some bulk unpasteurized milk supplies; and 
that antibiotics are available to treat this disease. However, 
treatment of chronic Q fever caused by C. burnetii requires antibiotic 
regimens that can last for periods up to several years. This long-term 
treatment is associated with significant adverse effects and relapse is 
common upon withdrawal of the treatment (Ref 23). The determination to 
retain C. burnetii on the HHS list of select agents and toxins is based 
on multiple factors, including its environmental stability, ease of 
transmission to humans, extremely low infectious dose, high morbidity, 
its ability to incapacitate large numbers of people, and its prior 
history of weaponization. Historical records indicate that extensive 
development occurred in the use of this agent as an incapacitating 
weapon.
Retention of Diacetoxyscirpenol, Saxitoxin, T-2, and Tetrodotoxin 
Toxins
    We proposed the retention of Diacetoxyscirpenol, Saxitoxin, T-2 
toxin, and Tetrodotoxin on the HHS list of select agents and toxins. 
One commenter recommended the removal of these toxins along with Shiga-
like ribosome inactivating proteins, Shigatoxin, Conotoxins, and C. 
perfringens epsilon toxin. This commenter stated that ``continuing to 
include these toxins on the select agent list has unintended 
consequences such as the U.S. Department of Transportation (USDOT) 
policies regarding shipment of infectious substances that extends the 
list to agents, such as E. coli that produce these toxins, which 
results in limiting shipments to public health laboratories.''
    Although Shigatoxin producing strains of Escherichia coli are not 
subject to the select agent regulations, the removal of Shigatoxin and 
Shiga-like ribosome inactivating proteins should positively address the 
commenter's concern regarding the USDOT policies. We do not agree with 
the commenter that Saxitoxin, T-2 toxin, Tetrodotoxin, and 
Diacetoxyscirpenol should be removed from the list. Significant factors 
considered in our determination to retain these toxins are their acute 
human toxicity, the lack of medical countermeasures or specific 
antidotes, and the stability of the toxins in a variety of different 
matrices including foodstuffs.
    With respect to the comment expressing concerns about the 
regulation of E. coli strains that produce these toxins, it should be 
noted that nucleic acids that encode for the functional form(s) of 
select toxins, if the nucleic acids can be expressed in vivo or in 
vitro or are in a vector or recombinant host genome and can be 
expressed in vivo or in vitro, are subject to the regulations (See 
Sec.  73.3(c)(2)). We consider it important to regulate E. coli strains 
that have been modified to produce these materials since they are 
capable of producing significant quantities of select toxins. It should 
also be noted that E. coli strains that do not contain nucleic acids 
that encode for the functional form(s) of select toxins are not subject 
to these regulations.
Retention of Yersinia pestis
    We proposed to retain Y. pestis on the HHS select agents and toxins 
list based on our scientific conclusion regarding the bacterium's high 
mortality rate, ease of dissemination and production, and person-to-
person transmission of Y. pestis infections. We received no comments 
regarding this proposal.
Overlap Select Agents and Toxins
Reorganization of Venezuelan Equine Encephalitis Virus (VEE)
    We proposed the removal of VEE subtypes ID and IE from the list of 
overlap select agents and toxins, with subtypes IAB and IC being 
retained on the list. Commenters recommended

[[Page 61091]]

removing the entire VEE group from the overlap select agent list 
because they believe that current subtyping assays for the 
identification of VEE are not sensitive enough to distinguish between 
these subtypes. One commenter stated that the subtype IC group can 
arise via a single mutation in the ID group and considering VEE's high 
mutation rates, an IC subtype can emerge from a laboratory using 
subtype ID strains. Commenters also noted that there are two vaccines 
available for humans. In addition, commenters argued that the mortality 
rate associated with VEE infections via the aerosol route may be very 
low.
    We made no changes to the overlap list of select agents and toxins 
based on these comments. Straightforward diagnostic molecular 
techniques, such as sequencing with subtype/variety specific polymerase 
chain reaction (PCR) primer sets or serological testing with specific 
monoclonal antibodies, can distinguish between enzootic and epizootic 
VEE. We also note that based on available data, the emergence of 
epidemic subtype 1C from subtype 1D is a rare event. In addition, while 
an equine vaccine is available for VEE, human vaccines are limited in 
supply and availability.
    While the listing found in section 4 (Overlap select agents and 
toxins) will read ``Venezuelan equine encephalitis virus,'' a new 
subparagraph (d)(3) in that same section excludes from regulation, any 
ID and IE serotypes of Venezuelan equine encephalitis virus provided 
that an individual or entity can verify that the Venezuelan equine 
encephalitis virus is either the ID or IE serotype.
Retention of Bacillus anthracis (Pasteur Strain)
    We proposed to designate B. anthracis as a Tier 1 select agent. A 
number of commenters objected to such a blanket designation, arguing 
instead that the B. anthracis Pasteur strain should be exempted from 
consideration either as a Tier 1 select agent or as a select agent in 
general.
    Commenters argued that because Laboratory Response Network (LRN) 
laboratories maintain live cultures of non-pathogenic B. anthracis 
Pasteur strain for use in quality control testing, designation of B. 
anthracis as a Tier 1 select agent would have the potential to impact 
the willingness or ability of LRN laboratories to maintain inventories 
of B. anthracis Pasteur strain due to the perceived regulatory and 
financial burdens associated with the possession of Tier 1 select 
agents and toxins. The commenters went on to state that this situation 
could potentially impact national health and safety given that the 
potential use of B. anthracis spores as a bioweapon remains a viable 
threat. They also argued that the increased regulatory burdens, 
particularly on front-line diagnostic laboratories, could lead to an 
overall decrease in the number of laboratories that would otherwise 
serve to ensure the LRN has sufficient capacity to detect and respond 
to a deliberate release of B. anthracis.
    Commenters stated that the B. anthracis Pasteur strain is analogous 
to the B. anthracis Sterne strain, which has already been excluded 
pursuant to section 4(e) of the select agent regulations because it was 
determined not to pose a severe threat to public health and safety, 
animal health, or animal products. The commenters argued that B. 
anthracis Pasteur strain should not be considered as a select agent 
given that the only way to create an agent that poses a severe threat 
would be to combine the Pasteur strain with a non-regulated strain. The 
commenters pointed out that other agents that pose little harm 
individually, but could be modified genetically to become harmful, are 
not included on the select agent list because of this potential threat.
    Another commenter claimed that the designation of B. anthracis 
Pasteur strain as a select agent would not serve to prevent an 
authorized person from intentionally or accidentally facilitating the 
combination of plasmids from Sterne and Pasteur types of strains to 
create a wild type phenotype. The commenter stated that combining these 
two strains can be accomplished no matter what sort of physical 
security may be employed to prevent access, theft, loss, or release of 
the agent. The commenter concluded that more effective preventive 
measures can be achieved through training and educating microbiologists 
on how to avoid accidentally combining these two strains and by 
penalizing any individuals who intentionally try to combine them.
    We only agree in part with the commenters that it does not meet the 
Tier 1 designation, but do not agree to removing it from the select 
agent list altogether.
    While we agree that the Pasteur strain does not meet the criteria 
for inclusion as a Tier 1 select agent, we believe that retaining the 
Pasteur strain as a select agent will allow for continued oversight of 
laboratories in which the accidental (or intentional) combination of 
this strain with the Sterne strain could occur to produce the wild type 
phenotype B. anthracis de novo. Failure to retain the Pasteur strain as 
a select agent could result in an environment in which the probability 
of creating virulent wild type B. anthracis strains by the combination 
of non-regulated strains would be enhanced. Therefore, we have chosen 
not to exclude the Pasteur strain from the overlap list of select 
agents in this rulemaking. We will continue to evaluate exclusion 
requests as additional information becomes available in this area.
Retention of Brucella abortus, Brucella melitensis, and Brucella suis
    We proposed to retain B. abortus, B. melitensis, and B. suis on the 
overlap list of select agents and toxins based on the bacteria's ease 
of production, high infectivity via the aerosol route, low infectious 
dose, and lack of brucellosis vaccines currently available for humans 
in the United States. We received no comments based on this proposal 
and will be retaining B. abortus, B. melitensis, and B. suis on the 
overlap list of select agents and toxins.
Retention of Burkholderia mallei
    We proposed to retain B. mallei on the overlap list of select 
agents and toxins based on our determination that the bacteria can be 
easily produced in large quantity and transmitted via the aerosol 
route. In addition, the mortality rate for untreated cases of glanders 
is high, and given the rarity of this disease in the United States, 
experience in the diagnosis and treatment is limited. We received no 
comments based on this proposal and will be retaining B. mallei on the 
overlap list of select agents and toxins.
Retention of Burkholderia pseudomallei
    We proposed the designation of B. pseudomallei as a Tier 1 select 
agent. Commenters stated that B. pseudomallei should not be a select 
agent based on the following criteria:
     The criteria by which Coccidioides were proposed by HHS/
CDC to be removed from the list;
     B. pseudomallei is non-communicable from person-to-person;
     B. pseudomallei lacks a history of use or development as a 
successful biologic weapon (as compared with B. mallei, a highly 
pathogenic organism with which B. pseudomallei is inappropriately 
linked in the list);
     B. pseudomallei has a low incidence of symptomatic disease 
following natural infection; and
     The outcome of 99.9 percent of infections with B. 
pseudomallei is asymptomatic infection. Life-threatening illness occurs 
only in a few

[[Page 61092]]

hosts with particular risk factors, particularly renal failure and 
diabetes.
    We disagree with the commenters that B. pseudomallei should be 
removed from the overlap list of select agents and toxins. Significant 
factors in our determination include the fact that B. pseudomallei is 
as virulent in animal models as B. mallei, B. pseudomallei is not 
endemic in the United States, B. pseudomallei has a low infectious 
dose, B. pseudomallei possesses robust environmental stability, and 
timely diagnosis may be complicated because of the rareness of disease 
in the United States. In addressing the comment referring to the 
criteria used to remove Coccidioides, we note the availability of 
licensed treatments for Coccidioides infection and a lowering of our 
assessment of the impact of Coccidioides infection on human health as 
indicated by the high proportion of subclinical cases observed in 
endemic areas. We do not believe that these factors apply to B. 
pseudomallei. In addition, we note that B. pseudomallei is not 
extensively endemic in the United States as are Coccidioides species. 
Therefore, we are retaining B. pseudomallei on the overlap list of 
select agents and toxins.

B. Tiering of Select Agents and Toxins

    On July 2, 2010, President Obama signed Executive Order 13546 
``Optimizing the Security of Biological Select Agents and Toxins in the 
United States'' that directed the HHS Secretary to designate a subset 
of the select agents and toxins list (Tier 1) that presents the 
greatest risk of deliberate misuse with the most significant potential 
for mass casualties or devastating effects to the economy, critical 
infrastructure, or public confidence. In the development of the Tier 1 
subset, care was used to balance risks identified in Executive Order 
13546 with the Congressional mandate found in the Public Health 
Security and Bioterrorism Preparedness and Response Act of 2002 (42 
U.S.C. 262a) to ensure the availability of select agents and toxins for 
research, education, and other legitimate purposes. Executive Order 
13546 also established the FESAP to advise the HHS Secretary on the 
designation of Tier 1 agents and toxins, reduction in the number of 
agents on the select agent list, establishment of suitability standards 
for those having access to Tier 1 select agents and toxins, and the 
establishment of physical security and information security standards 
for Tier 1 select agents and toxins. Tiering of the select agents and 
toxins list will allow for the application of optimized security 
measures for those select agents or toxins which pose a higher risk to 
public health and safety. A two-part risk analysis was conducted by the 
FESAP on each select agent and toxin on the list. First, experts in the 
biology of these agents and toxins evaluated their ``potential for mass 
casualties or devastating effects to the economy, critical 
infrastructure, or public confidence.'' This included assessments of 
morbidity and mortality, communicability, infectious dose, availability 
of countermeasures, and estimated economic impact of a potential 
attack. Second, each agent and toxin was assessed by experts from the 
DOD, DHS, and Department of Justice (DOJ) for its ``risk of deliberate 
misuse,'' including its history of weaponization and/or known interest 
by state or non-state adversaries. In addition, the Federal Select 
Agent Program also used information obtained from DHS Material Threat 
Determinations in making final decisions regarding their 
recommendations as to which select agent or toxin should be designated 
as Tier 1. These evaluations in combination with (1) input from public 
comments received in response to the NPRM, and (2) relevant findings in 
recent government and non-government reports, informed the 
deliberations on which agents should be designated as Tier 1, as well 
as those that should be removed from the select agent and toxin list. 
Agents that scored highly on both the public health and biothreat sets 
of criteria were judged to be those that met the criteria for Tier 1. 
We have determined that the following agents should be designated as 
Tier 1 agents: B. anthracis, Botulinum neurotoxins, Botulinum 
neurotoxin producing species of Clostridium, B. mallei, B. 
pseudomallei, Ebola virus, F. tularensis, Marburg virus, Variola major 
virus, Variola minor virus, and Y. pestis.
    Commenters questioned why we believe that the current regulations 
were not sufficient to contain, secure, and protect the proposed Tier 1 
select agents and toxins from theft, loss, exposure, or release. In 
response, we note that the absence of clearly defined, risk-based 
security measures in the select agent regulations raised concern both 
by stakeholders within the Executive Branch and outside the government. 
This is the focus of Executive Order 13486 (Strengthening Laboratory 
Biosecurity in the United States) and Executive Order 13546 (Optimizing 
the Security of Biological Select Agents and Toxins in the United 
States) that call for improvements in select agent security and risk 
management. The additional security requirements for those entities 
possessing Tier 1 select agents and toxins will enhance physical 
security, personnel suitability, and information security within the 
affected entities.
    The commenters further contended that the proposed regulatory 
changes failed to achieve the goal of minimizing the impact of the 
regulations on the legitimate uses of select agents and toxins that 
Executive Order 13546 notes are essential to national security. In 
response, we note that the overall number of select agents and toxins 
has been reduced, lessening the overall regulatory burden. In addition, 
by maintaining a performance-based approach in the regulations, we are 
allowing regulated entities to develop policies and procedures that 
meet the new requirements of the regulations while accommodating 
specific operational aspects of each entity.
    Other commenters stated that the proposed tiering system poses 
significant questions as to the nature of the risk assessment process. 
Specifically, commenters questioned listing as Tier 1 agents bacterial 
diseases that are treated with licensed antibiotics, that are not 
commonly spread person-to-person, and that are present in the 
environment of the United States; while viruses that have no known 
therapy and that pose extreme risk to western populations are absent 
from the Tier 1 list. The commenters believed that the 20 criteria used 
for evaluation of each select agent and toxin should be made available 
to the regulated community for review and assessment. We note that the 
20 criteria referenced by the commenters were the ones used by the 
FESAP in providing recommendations to the Federal Select Agent Program. 
Nevertheless, we agree with the commenters that it is reasonable to 
publish the criteria used by the FESAP in providing the tiering 
recommendations to the Federal Select Agent Program. These criteria 
are:
    1. The relative ease with which a select agent or toxin might be 
acquired from a laboratory or commercial source;
    2. The relative ease of production of a select agent or toxin;
    3. The relative ease by which a select agent or toxin might be 
modified in order to enhance its pathogenicity, transmissibility, or 
ability to evade medical and non-medical countermeasures;
    4. The potential for easy deliberate dissemination;
    5. The potential for creating disease or illness;
    6. The relative environmental stability of a select agent or toxin 
by itself and how well it survives in the environment

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in which it is formulated or disseminated;
    7. The amount of select agent or toxin necessary to induce illness;
    8. The relative ease with which a particular select agent or toxin 
might be disseminated or transmitted from one animal or person to 
another or into the environment where it could produce a deleterious 
effect upon animal, plant, or human health;
    9. Whether the target population has innate immunity to the select 
agent or toxin or whether immunity has been acquired from a source such 
as vaccines;
    10. The potential for the select agent or toxin to create morbidity 
(i.e., any non-fatal illness that renders partial dysfunction to an 
animal or human lasting weeks or months that will eventually resolve 
with medical, veterinary, and/or supportive care);
    11. The burden placed on the human, veterinary, or plant health 
system by the deliberate release of the select agent or toxin;
    12. The ability to detect a release of the select agent or toxin 
into the environment, food, water, or soil;
    13. The ability of the human and agricultural health authorities to 
accurately and rapidly diagnose and treat the disease presented by a 
release of the select agent or toxin;
    14. The existence of countermeasures to prevent, treat, or mitigate 
the symptoms of a disease caused by the release of a select agent or 
toxin and/or its spread through a population;
    15. The potential for high animal, plant, or human mortality rates 
with delivery of medical countermeasures;
    16. The potential for high animal, plant, or human mortality rates 
without delivery of medical countermeasures;
    17. The short-term economic impact of a single outbreak of a 
disease or release of a toxin;
    18. The human, monetary, and other resource costs of making an 
area, building, industrial plant, farm, or field safe for humans, 
animals or plants to inhabit following the release of the select agent 
or toxin;
    19. The pathogen's ability to persist in the environment or to find 
a reservoir that makes its recurrence more likely; and
    20. The long-term health or economic consequences caused by a 
single release of the select agent or toxin.
    Commenters argued that if there is a ``Tier 1'' designation of 
certain select agents and toxins, there logically should be a list of 
designated ``Tier 2'' select agents and toxins. We made no changes 
based on this comment. In designating certain select agents and toxins 
as ``Tier 1,'' the Federal Select Agent Program considered and rejected 
the idea of designating the remaining agents as ``Tier 2'' because the 
establishment of the Tier 1 category is in no way intended to imply 
that the agents not designated as Tier 1 pose a lesser risk to public 
health and safety than they have previously. Further, we believe that 
the establishment of more varying levels of risk categories would 
create an increased administrative oversight burden and needless 
complications for regulated entities.
    Various commenters argued that the following select agents should 
be not be listed as Tier 1 agents: F. tularensis, Y. pestis, B. mallei, 
B. pseudomallei, and B. anthracis because these bacteria are all 
readily found in the environment and treated effectively with 
antibiotics, such that additional security requirements will have 
little or no effect on biodefense. Commenters said they recognized that 
public perception must be taken into account, but they stated a belief 
that there is little public recognition of many of these bacteria as 
potential biothreat agents. Commenters stated that F. tularensis is not 
transmissible from one human to another nor does it have either the 
potential for major human health impact or the potential for a high 
mortality rate.
    Based on the FESAP recommendation using the criteria identified 
above, we disagree with the commenters that F. tularensis should not be 
designated as a Tier I select agent. Significant factors that we 
considered include the low infectious dose, the robust environmental 
stability, and a well-documented history of weaponization associated 
with this agent.
    Commenters stated that B. pseudomallei should be not be listed as 
Tier 1 agent because B. pseudomallei is non-communicable from person-
to-person, lacks a history of use or development as a successful 
biologic weapon (as compared with B. mallei, a highly pathogenic 
organism with which B. pseudomallei is inappropriately linked in the 
list), and has a low incidence of symptomatic disease following natural 
infection. The outcome of 99.9 percent of infections with B. 
pseudomallei is asymptomatic infection. Life-threatening illness occurs 
only in a few hosts with particular risk factors, particularly renal 
failure and diabetes.
    Based on the FESAP recommendation using the criteria identified 
above, we disagree with the commenters that B. pseudomallei should not 
be designated as a Tier I select agent. Significant factors in our 
determination include the fact that B. pseudomallei is as virulent in 
animal models as B. mallei, B. pseudomallei is not endemic in the 
United States, B. pseudomallei has a low infectious dose, B. 
pseudomallei possesses robust environmental stability, and timely 
diagnosis may be complicated due to the rareness of disease in the 
United States. In addressing the comment referring to the criteria used 
to remove Coccidioides, we note the availability of licensed treatments 
for Coccidioides infection and a lowering of our assessment of the 
impact of Coccidioides infection on human health, as indicated by the 
high proportion of subclinical cases observed in endemic areas. We do 
not believe that this applies to B. pseudomallei. In addition, we note 
that B. pseudomallei is not extensively endemic in the United States as 
are Coccidioides species. Therefore, B. pseudomallei will be listed as 
a Tier 1 select agent and toxin.
    Commenters stated that Botulinum toxin should not be identified as 
a Tier 1 agent because Botulinum toxin is a non-replicating, non-
infectious chemical agent and should not be in the same category as 
highly contagious biological agents such as B. anthracis or un-
treatable agents such as the Ebola virus. We made no changes based on 
these comments. We are aware that Botulinum toxin is a non-replicating 
and non-infectious toxin. However, the rule seeks to balance the 
regulatory oversight of agents and toxins that have the potential to 
pose a severe threat to public health and safety while maintaining 
availability of these agents and toxins for research and educational 
activities. Another commenter further argued that Botulinum neurotoxin 
quantities in excess of 500 microgram ([mu]g) should be designated as 
Tier 1 toxin, but quantities of less than 500 [mu]g should not be 
regulated. One commenter questioned the ``logic (or science)'' behind 
this decision, particularly when pharmaceutical production facilities 
possessing greater than 500 [mu]g will be exempt from the new 
regulations.
    We noted that the pharmaceutical production facilities possessing 
select agent or toxins are currently regulated under select agent 
regulations. However, products that are, bear, or contain listed select 
agents or toxins that are cleared, approved, licensed, or registered 
under any of the laws specified in Section 5(c) and 6(c) of the 
regulations are exempted from the requirements of the select agent 
regulations, insofar as their use is only for the approved purpose and 
meets the requirements of such laws. The exemption would only apply to 
the final product created from or containing the select agent or toxin. 
The amount of each toxin that could be possessed

[[Page 61094]]

without regulation by a principal investigator, a treating physician or 
veterinarian, or a commercial manufacture or distributor was determined 
on the basis of toxin potency and how much one could safely possess 
without constituting a potential threat to public safety or raising 
concerns about use as a weapon that would have a widespread effect. The 
level specified in the rule was determined after consultation with 
subject matter experts on this toxin. The determination that a toxin 
posed a severe public health threat was based on the ability for the 
mass distribution of the toxin for mass casualty purposes. Therefore 
Botulinum neurotoxin will be placed on the HHS Tier 1 list of select 
agents and toxins.
    Commenters stated that Ebola and Marburg viruses should be removed 
from Tier 1 because none of the other hemorrhagic fever viruses are in 
Tier 1, yet they are just as dangerous. We disagree with the commenters 
and note that the hemorrhagic viruses on the select agent list exhibit 
distinct differences in morbidity, mortality, transmissibility, and 
degree of pathogenicity. Therefore our consideration to designate a 
particular virus as Tier 1 is made on a virus-by-virus basis. Ebola 
virus and Marburg virus are designated as Tier 1 select agents.
Reconstructed Replication Competent Forms of the 1918 Pandemic 
Influenza Virus Containing Any Portion of the Coding Regions of all 
Eight Gene Segments (Reconstructed 1918 Influenza Virus)
    One commenter argued that Reconstructed 1918 Influenza virus should 
be a Tier 1 select agent since it is a pathogenic agent not currently 
present in any human population and not currently present in any 
natural environment. The commenter further argued this agent exhibited 
high transmissibility and high lethality and caused a global pandemic 
with massive mortality (>=50 million deaths; >=3 percent of the human 
population at the time), massive economic impact, and major 
psychological impact when last present in human populations.
    We did not propose to designate Reconstructed 1918 Influenza virus 
as a Tier 1 select agent and are making no changes to the HHS list of 
select agents and toxins based on this comment. Recent studies have 
increased our understanding of the public health risks associated with 
this agent. Current reports suggest that as much as 60 percent of the 
population in the United States may have some immunity to the 1918 
Influenza virus. We also considered the potential availability of 
vaccines and antiviral treatments when considering whether to designate 
this virus as a Tier 1 select agent.
    Although we did not designate the Reconstructed 1918 Influenza 
virus as a Tier I select agent, we retained this virus as a select 
agent. In retaining this virus as a select agent we recognize that, to 
the best of our knowledge, the only place the Reconstructed 1918 
Influenza virus currently resides is in laboratories. Unlike other 
influenza viruses, the most likely source of a Reconstructed 1918 
Influenza virus outbreak would be as a result of a breach or failure of 
a laboratory's biosafety or biosecurity program.
Diagnostic Laboratories and Tier 1 Agents
    Commenters have expressed concerns about the ability of diagnostic 
laboratories, such as those in the LRN, to retain their ability to 
perform diagnostics while meeting the requirements for Tier 1 select 
agents and toxins. The Federal Select Agent Program recognizes the 
critical role of diagnostic laboratories in the early detection and 
response to outbreaks of disease in humans and agriculture. While all 
of the Tier 1 regulatory requirements will apply to laboratories that 
maintain permanent stocks of Tier 1 select agents and toxins, 
laboratories may wish to consider maintaining their proficiency in 
detecting Tier 1 select agents and toxins through the use of excluded 
attenuated strains of select agents and toxins that meet their testing 
requirements. Examples of excluded attenuated strains include: B. 
anthracis strains devoid of the plasmid pX02 (e.g., B. anthracis 
Sterne, pX01+pX02-) (effective 2-27-2003), F. tularensis subspecies 
holartica LVS (live vaccine strain; includes NDBR 101 lots, TSI-GSD 
lots, and ATCC 29684) (effective 2-27-2003), and Y. pestis strains 
(e.g., Tjiwidej S and CDC A1122) devoid of the 75 kb low-calcium 
response (Lcr) virulence plasmid (effective 2-27-2003). Possession of 
an excluded attenuated strain, so long as it has not been subjected to 
any manipulation that restores or enhances its virulence, would be 
excluded from the HHS and USDA select agent regulations. Those 
laboratories encountering a Tier 1 select agent or toxin in their 
routine work with diagnostic or proficiency testing, would still 
qualify for the clinical or diagnostic laboratory exemption found in 
sections 5(a) and 6(a) of the regulations. Should a diagnostic 
laboratory wish to maintain a select agent identified in a diagnostic 
sample longer than the seven calendar days currently allowed by the 
select agent regulations, the diagnostic laboratory can request that 
HHS/CDC or USDA/APHIS grant additional time before the select agent is 
transferred or destroyed pursuant to either section 5(a) or section 
6(a) of the regulations.

C. Responses to Other Proposed Changes

    With respect to the remainder of the sections outlined below, the 
following changes are based on comments received in response to the 
NPRM and recommendations from the FESAP. We updated the Web address 
throughout the document as all information concerning the Federal 
Select Agent Program is now centralized on the National Select Agent 
Registry (NSAR) at http://www.selectagents.gov/. In addition, HHS/CDC 
and USDA/APHIS used similar language in our final rules to ensure 
consistency between the regulations.
Definitions
Occupational Exposure
    We proposed to add a definition for occupational exposure based on 
the definition used in the Occupational Safety and Health 
Administration (OSHA) regulations found in 29 CFR 1910.1030 (Bloodborne 
pathogens). Commenters proposed that we not use the OSHA definition 
since the adoption of this definition would limit possible exposures to 
select agents only to bloodborne pathogens and to other potentially 
infectious materials as noted in that standard, but not to occupational 
exposure to aerosols of the agents in the select agent list. One 
commenter recommended ``a definition, which combines the OSHA 
bloodborne pathogens standard and the definition of ``exposure 
incident'' found in the Bloodborne Pathogen Standard and Exposure 
Incident (Laboratory) from the Cal/OSHA Aerosol Transmissible Diseases 
(California Code of Regulations, Title 8, Section 5199), to ensure that 
both non-aerosol and aerosol exposure events are appropriately 
addressed that would state ``Exposure Incident: Any event which results 
in (1) an individual experiencing a specific eye, mouth, or other 
mucous membrane, non-intact skin, or parenteral contact with a select 
agent or toxin; or (2) an individual experiencing a potential exposure 
to an aerosolized select agent without the benefit of appropriate 
exposure controls, and the circumstances of the aerosol exposure make 
the transmission of a disease sufficiently likely that the individual 
requires further medical evaluation by a

[[Page 61095]]

Physician or other licensed health care professional.'' We agree with 
the commenters and are revising the definition to state: ``Any 
reasonably anticipated skin, eye, mucous membrane, parenteral contact, 
or respiratory aerosol exposure to select agents or toxins that may 
result from the performance of an employee's duties.''
Recombinant and Synthetic Nucleic Acids
    We proposed to add the definitions for recombinant and synthetic 
nucleic acids to the regulations. One commenter stated that the broad 
definition has implications in all areas of synthetic biology 
technology, including industrial enzymes, renewable chemicals for 
pharmaceutical and industrial applications, biobased products, personal 
care products, renewable specialty chemicals, biofuels, and healthcare 
products. The commenter argued that the consequences of such a 
definition could impede the growth of sustainable products from an 
emerging science such as synthetic biology technology. The commenter 
recommended that we not adopt the new definitions of recombinant and 
synthetic nucleic acids as put forth in the proposed rule because the 
existing language of the regulation is sufficient to cover the uses of 
synthetic nucleic acids as currently practiced; and furthermore, that 
the proposed definitions utilize language that was proposed to, but 
rejected by, the NIH Recombinant DNA Advisory Committee (NIH-RAC). The 
commenter further argued that if we feel compelled to introduce a new 
definition, that we follow the leadership of the NIH-RAC and promulgate 
a simpler definition that is not focused on the underlying mechanism of 
production of the nucleic acids. We made no changes to the definition 
based on this comment. The scope of our oversight is limited by the 
list of select agents and toxins and therefore does not extend to all 
synthetic biology. We have updated the organization of the definitions 
of recombinant and synthetic nucleic acids upon consultation with the 
NIH Office of Biotechnology Activities. The definitions now read as:
     Recombinant nucleic acids. (a) Molecules that are 
constructed by joining nucleic acid molecules and that can replicate in 
a living cell (i.e., recombinant nucleic acids) or (b) molecules that 
result from the replication of those described in (a) above.
     Synthetic nucleic acids. (a) Molecules that are chemically 
or by other means synthesized or amplified, including those that are 
chemically or otherwise modified but can base pair with naturally 
occurring nucleic acid molecules (i.e., synthetic nucleic acids) or (b) 
or molecules that result from the replication of those described in (a) 
above.
    In addition, we have separated the definition of recombinant and 
synthetic nucleic acids for clarity.
Restricted Person
    We proposed to add the definitions for the following terms in 42 
CFR 73.1, to clarify the criteria related to the identification of a 
restricted person: Adjudicated as a mental defective, Alien, Committed 
to any mental institution, Controlled substance, Crime punishable by 
imprisonment for a term exceeding 1 year, Indictment, Lawfully admitted 
for permanent residence, Mental institution, Restricted person, and 
Unlawful user of any controlled substance. Commenters stated that 
proposed definitions need to be further clarified and are overly 
restrictive or vague. We agree with these comments and are not 
including these definitions in this final rule.
Exclusions
    We proposed to remove language stating that an attenuated strain of 
a select agent that had been granted an exclusion because it did not 
pose a severe threat to public health and safety would be published in 
the Federal Register. We received no comments regarding this proposal. 
However, one commenter requested clarification regarding previously 
established exclusions as currently listed on the NSAR at http://www.selectagent.gov/Select%20Agents%20and%20Toxins%20Exclusions.html. 
The commenter stated that individuals should not have to reapply and 
secure written approval for those attenuated strains that were 
previously recognized as excluded from select agent status.
    In response to this commenter, we note that the language posted on 
the Federal Select Agent Program Web site at http://www.selectagent.gov/Select%20Agents%20and%20Toxins%20Exclusions.html 
already clarifies that once an attenuated strain of a select agent (or 
an inactivated select toxin) is determined not subject to the 
requirements of select agent regulations, the strain or toxin will only 
be subject to regulation if there is any modification such that 
virulence is restored or enhanced. Therefore, individuals are not 
required to reapply and seek written approval for attenuated strains or 
inactive toxins that have already been determined by the Federal Select 
Agent Program to be excluded.
    As noted earlier, we proposed the removal of the South America 
genotypes of EEEV and the VEEV subtypes ID and IE. We have also 
excluded the West African clade of Monkeypox virus. To prevent 
confusion on how an entity should handle samples that have been 
determined to be within a general taxonomic classification (e.g., EEEV) 
but not within a particular genotype or subtype (e.g., NA-EEEV), we 
have maintained the current general taxonomic listing of HHS and 
overlap select agents as opposed to listing a specific strain and added 
an exemption for the strains, subtypes, or pathogenicity levels which 
are not considered to have the potential to pose a severe threat to 
public health and safety. With this change, we believe we have 
clarified that when an agent is initially identified by taxonomic 
classification it is subject to the select agent regulations until 
further testing is accomplished to exclude the particular agent by 
strain, subtype, or pathogenicity level. We believe it is important 
that laboratories should treat these select agents and toxins as though 
they must comply with this part until further testing can be conducted 
to verify whether the agent is indeed an excluded strain, subtype, or 
pathogenicity level. This change should not have any impact on the 
exemption for diagnostic laboratories or alter the process of taking in 
diagnostic samples and forwarding any potentially identified select 
agents for further testing. It also does not change the reporting 
criteria for when the agent is confirmed as a select agent. Therefore, 
we are maintaining the listing of select agents in 42 CFR 73.3(b) to 
read, Monkeypox virus and Eastern Equine Encephalitis virus, and adding 
the following criteria to be excluded in 42 CFR 73.3(d)(5): Any South 
American genotypes of Eastern Equine Encephalitis virus and any West 
African Clade strains of Monkeypox virus. We are also amending the 
proposed list of select agents in 42 CFR 73.4(b) to read Venezuelan 
equine encephalitis virus, and adding the following criteria to be 
excluded in 42 CFR 73.4(d)(3): Any ID and IE subtypes of Venezuelan 
equine encephalitis virus.
Toxins
    In 42 CFR 73.3(e) and 73.4(e), we proposed to clarify that the 
``inactive form of a select toxin'' may be excluded from regulation 
since the current term, ``attenuated strain of toxin'' is 
scientifically inaccurate. We received comments that were supportive of 
this

[[Page 61096]]

proposed change and will finalize the change in this rule.
    We proposed to add 42 CFR 73.3(d)(4) which would state, ``An animal 
inoculated with or exposed to an HHS select toxin.'' The change allows 
animals injected with or exposed to a select toxin not to be considered 
a ``select toxin.'' Therefore, the animals would not need to be housed 
in a registered space. The change eliminates an unnecessary burden on a 
registered entity because recovering the toxin from within an animal 
subject is highly difficult and such removal is unlikely to produce a 
reasonable yield of recovery. In addition, there is uncertainty as to 
whether the toxin would remain active when recovered from the animal. 
For these reasons, it is highly unlikely that once introduced into an 
animal, sufficient toxin would be able to be recovered to pose a 
significant hazard to public health. We received comments that were 
supportive of this proposed change.
    One commenter recommended that we clarify that the aggregate amount 
in Sec.  73.3(d)(3) is per ``principal investigator, treating physician 
or veterinarian, or commercial manufacturer or distributor,'' and not 
per entity. We made no changes to the regulations based on this comment 
because the current regulatory language provides sufficient protections 
against the unrecognized accumulation of regulated quantities of select 
toxins at a given entity through multiple procurements of less than 
threshold amounts by multiple principal investigators within the 
entity. The same commenter recommended that we amend the regulatory 
language from ``toxin'' to ``purified toxin.'' The commenter argued 
that since there are naturally occurring organisms that produce these 
toxins, unless they are purified they will pose only a low-level risk 
to human health. We made no changes to the regulation based on this 
comment since any HHS select agent or toxin that is in its naturally 
occurring environment, provided the select agent or toxin has not been 
intentionally introduced, cultivated, collected, or otherwise extracted 
from its natural source, is already excluded in section 73.3. The same 
commenter also recommended that the guidance be clarified to state that 
there are some select toxin-producing organisms that are not covered 
under this section of the regulations. Although we agree that there are 
indeed toxin-producing organisms that are not covered under this 
section of the regulations, we made no changes to the regulation based 
on this comment. The regulations clearly state which agents are 
regulated. Guidance is also available on the select agent Web site 
(http://www.selectagent.gov/SyntheticGenomics.html) and defines the 
select agents that are regulated.
Due Diligence
    We proposed to require that an entity transferring a toxin in 
amounts which would otherwise be excluded from the provisions in 42 CFR 
part 73 would be excluded only if the transferor: (1) Uses due 
diligence and documents that the recipient has a legitimate need (i.e., 
reasonably justified by a prophylactic, protective, bona fide research, 
or other peaceful purpose) to handle or use such toxin; and (2) reports 
to HHS/CDC if they detect a known or suspected violation of Federal law 
or become aware of suspicious activity related to the toxin. The 
majority of our commenters from academic institutions argued that the 
proposed toxin due diligence provisions did not improve the safety and 
security of excluded quantities of these toxins. The commenters 
expressed concerns that if the toxin is being transferred to an 
individual employed by an entity which clearly has a bona fide research 
purpose, the laboratory providing the material should not have an 
obligation to report the transfer. Commenters further requested that 
the terms, ``due diligence'' and ``legitimate need'' be clarified. We 
made no changes to the regulation based on these comments. The proposed 
amended regulatory language to require due diligence and the reporting 
of known or suspected violations of Federal law in this case addresses 
concerns that an individual may be able to accumulate, unnoticed by 
anyone, regulated amounts of a select toxin by stockpiling shipments of 
unregulated amounts. We believe that commercial manufacturers and 
distributors already track the shipments of toxins as part of their 
quality management systems. We note that entities registered with the 
Federal Select Agent Program are already required to maintain records 
of internal toxin transfers. We are not defining either ``due 
diligence'' or ``legitimate need'' in the regulatory language because 
we believe both of these terms to be widely used and commonly 
understood. We would expect that, before transferring any amount of a 
select toxin, a reasonable person would satisfy themselves that the 
recipient had a legitimate need for a prophylactic, protective, bona 
fide research, or other peaceful purpose. We also note that while the 
transfer has to be recorded, the only report required by the new 
regulatory language is a report of a transfer believed or suspected to 
be a violation of law.
Exemptions
Immediate Notification of the Identification of a Select Agent or Toxin 
Contained in a Specimen Presented for Diagnosis or Verification
    We proposed to amend 42 CFR 73.5 and 73.6 to limit the immediate 
notification requirement to only those select agents and toxins 
identified as Tier 1 agents and toxins because these agents and toxins 
present the greatest risk of deliberate misuse with the most 
significant potential for mass casualties. We received comments that 
were supportive of this proposed change and we are finalizing this 
requirement in this rule.
Public Health Emergency
    To eliminate an unnecessary burden on any individual or entity 
responding to a domestic or foreign public health emergency, we have 
removed the provision that the individual or entity must complete an 
APHIS/CDC Form 5 to request an exemption. Guidance on requesting an 
exemption for an individual or entity to respond to a domestic or 
foreign public health emergency may be found on the select agent Web 
site at www.selectagents.gov.
Responsible Official
Alternate Responsible Official
    We proposed to add language to clarify the role of an alternate 
Responsible Official in order to definitively establish that an 
alternate Responsible Official must have the full knowledge and 
authority to act for the Responsible Official in his/her absence. While 
commenters generally agreed, one commenter argued that the proposed 
changes would prohibit consultants from serving as an alternate 
Responsible Official. We are making no changes to the regulation in 
response to this comment. We first note that in the absence of the 
Responsible Official, a person who has been designated by the entity as 
an alternate Responsible Official becomes the entity's Responsible 
Official. We believe that an individual acting as a consultant would 
have neither the institutional authority nor responsibility to allow 
them to serve as an alternate Responsible Official. This does not mean 
that an entity Responsible Official cannot utilize the services of a 
consultant in carrying out his or her duties. But the regulations were 
designed to require an entity to vest authority and responsibility for 
ensuring compliance with the select

[[Page 61097]]

agent regulations in one entity official so that the person can take 
action in the name of the entity and on behalf of the entity, and not 
merely provide advice or consultation.
    Commenters also recommended that a provision for delegation of 
responsibilities to an alternate Responsible Official by the 
Responsible Official should be included, even with the Responsible 
Official present, so that an alternate Responsible Official would 
always be acting under the direction/oversight of the Responsible 
Official. Other commenters felt that it would be practical for the 
Responsible Official to delegate an alternate Responsible Official who 
is housed in the remote facility to take on the day-to-day 
responsibilities of the Responsible Official in that facility. We are 
making no changes to the regulations in response to these comments 
because the regulations already provide to the Responsible Official the 
flexibility to delegate the authority to perform certain tasks. While 
the regulations allow the Responsible Official as many assistants as 
he/she needs to ensure compliance with the regulations, the Responsible 
Official retains the ultimate responsibility for compliance. The 
regulatory provisions for the appointment of an alternate Responsible 
Official are in recognition of the fact that, as a practical matter, a 
single person cannot always be present at an entity. We believe that it 
is important for each entity to identify the person who has the 
responsibility for that entity to ensure compliance with the select 
agent regulations and this approach will help achieve a higher level of 
compliance than would be obtained from a system of shared 
responsibility.
Duty Station
    We proposed to add a requirement that the Responsible Official's 
regular place of employment or principal duty station must be located 
in close proximity to the physical location of the registered entity 
entered in section 1A of APHIS/CDC Form 1 (Application for Registration 
for Possession, Use, and Transfer of Select Agents and Toxins). As we 
stated in the preamble to the proposed rule, we believed that the 
Responsible Official should have a physical (and not merely a 
telephonic or audio/visual) presence at the entity to ensure that the 
entity is in compliance with the select agent regulations and be able 
to quickly respond to on-site incidents involving select agents and 
toxins. Commenters generally agreed with the requirement that the 
Responsible Official's regular place of employment or principal duty 
station must be co-located with the physical location of the registered 
entity entered in section 1A of APHIS/CDC Form 1. One commenter 
recommended that we eliminate the requirement for the definition 
because the Responsible Official is frequently a high-level 
administrator at a university, such as a Vice President for Research, 
and it would be infeasible in many cases for such a Responsible 
Official, whose duties extend beyond biosecurity, to be physically 
located at a registered entity; it would only add a layer of 
bureaucracy, which could detract from a focus on security, to require a 
second, on-site Responsible Official. We made no changes based on this 
comment. As noted above, the Responsible Official should be an 
individual who can perform all of the duties required for that 
position. The regulations were designed to place responsibility for 
ensuring compliance with the regulations in one position. However, some 
commenters requested that we clarify the provision regarding the 
individual's principal duty station, physical location, and ``close 
proximity with the physical location of the registered entity.'' In 
addition, one commenter requested that we explain how quickly the 
Responsible Official should be able to respond to onsite incidents in 
terms of turnaround time. Another commenter stated that they were not 
persuaded that ensuring compliance and a quick response to incidents 
are sufficient rationale for this requirement.
    In response, we are changing the language in section 73.9 to 
clearly state that the Responsible Official must have a physical (and 
not merely a telephonic or audio/visual) presence at the registered 
entity to ensure that the entity is in compliance with the select agent 
regulations and is able to quickly respond to on-site incidents 
involving select agents and toxins. We recognize that some entities are 
located on a campus with several registered laboratories situated in 
different buildings throughout the campus, and we believe it would be 
counterproductive to require that the Responsible Official be assigned 
to each physical laboratory listed on the entity's registration and 
require a set turnaround time to respond quickly to on-site incidents. 
However, the Responsible Official should be able to respond in a timely 
manner to onsite incidents in accordance with the entity's incident 
response plan. The regulations also contain a performance standard that 
the Responsible Official is physically located on the campus to ensure 
day-to-day oversight and compliance with the select agent regulations 
and to respond to any incident in a way that limits damage and ensures 
that select agents and toxins are secured and safeguarded.
Responsible Official Training Requirement
    We proposed to add a specific requirement that all Responsible 
Officials possess the appropriate training or expertise to execute 
their required duties. We received multiple comments and concerns about 
fulfilling the provisions of this proposed requirement. The breadth and 
variety of training and expertise available would be difficult to 
capture in regulatory language. Therefore, we will continue to assess 
the performance of the Responsible Official based on his or her 
efficacy in implementing the select agent and toxin regulatory 
requirements at the entity. As such, we have accepted these comments 
and have not included this provision in the final rule.
Access to Select Agents and Toxins
Timeframe
    We proposed to decrease the maximum length of time in which a 
Security Risk Assessment (SRA) will be valid from five years to three 
years in order to more expeditiously identify individuals who may have 
fallen into one of the prohibited or restricted categories. Commenters 
argued that our proposal to shorten this time period would increase the 
work load for individuals, entities, the Federal Select Agent Program, 
and the Federal Bureau of Investigation (FBI), and would only add 
bureaucratic expense for all without any source of compensation to the 
investigators and institutions who are endeavoring to contribute 
countermeasures against biothreats. Another commenter stated that it 
would have a significant impact on law enforcement's ability to handle 
the increased workload to conduct these investigations. One commenter 
was concerned that there would be delays in SRA approval that would 
negatively impact workload performance.
    We are making no changes to the regulations based on these 
comments. On January 9, 2009, the President signed E.O. 13486 entitled 
``Strengthening Laboratory Biosecurity in the United States.'' This 
Executive Order established a working group co-chaired by 
representatives of the DOD and HHS Secretaries. The scope of working 
group activities pertained to the policy of the United States that 
facilities that possess biological select agents and toxins have

[[Page 61098]]

appropriate security and personnel assurance practices to protect 
against theft, misuse, or diversion to unlawful activity of such agents 
and toxins. The working group provided final recommendations through 
careful consideration of proposals from subgroups and comments received 
from select agent entities and the public. The report is available at: 
http://orise.orau.gov/emi/scapa/files/biosecurity-report.pdf.
    One of the recommendations from the working group to enhance 
security was to perform the SRA every three years for all individuals 
with access to select agents and toxins instead of the existing policy 
of performing the SRA every five years. We concurred with this 
recommendation. Based on input from the FBI, we have determined that 
conducting SRA approvals every three years is beneficial in increasing 
the security of registered entities. As a policy matter, we have been 
processing SRAs on a three-year basis since June 1, 2011 and an 
increase in administrative burden has not been noted. We also did not 
receive any comments from the regulated community that they have 
experienced any additional burdens. Accordingly, we do not believe this 
regulatory change will result in an increased burden on registered 
entities.
Portability
    We also proposed to amend the regulations in section 73.10 to add 
new provisions by which individuals may have access to select agents 
and toxins at entities other than the individual's ``home'' entity. One 
commenter suggested that the Responsible Official, rather than the 
individual as proposed, make the request to the HHS Secretary or 
Administrator to approve access to select agents or toxins at another 
registered entity for a specific period of time. Other commenters 
requested clarification of the process and suggested that limiting 
access to only one entity at the time would be appropriate.
    In response to these comments, we are amending section 73.10 to 
provide that ``a person with a valid approval from the HHS Secretary or 
Administrator to have access to select agents and toxins may request, 
through his or her Responsible Official, that the HHS Secretary or 
Administrator provide their approved access status to another 
registered individual or entity for a specified period of time.''
    One commenter wanted clarification that an individual would have 
access to select agents at multiple registered entities based on the 
proposed language. The revised language would allow individuals the 
flexibility to have access to select agents and toxins at entities 
other than the individual's ``home'' entity. To address the commenter's 
concern that the SRA portability process is unclear, additional 
guidance has been developed and is available at http://www.selectagents.gov.
Security
Animals or Plants Accidentally or Intentionally Exposed to or Infected 
With a Select Agent
    One commenter was unclear regarding whether the security plan 
should contain procedures concerning animals or plants accidentally or 
intentionally exposed to or infected with a select toxin. We made no 
changes to the regulations based on this comment. As we discussed in 
the preamble for the NPRM, we are not requiring the security plan to 
address procedures concerning animals exposed to toxins because it is 
highly unlikely that once introduced into an animal, sufficient toxin 
can be recovered to pose a significant hazard to public health and 
safety.
    Another commenter wanted to know if the provision was for clinical, 
veterinary, or environmental laboratories performing diagnostic work to 
identify a select agent in humans, food or environmental samples. We 
made no changes to the regulation based on this comment. Any select 
agent or toxin that is in its naturally occurring environment (e.g., 
sand samples that are naturally infected with B. anthracis or milk 
samples that contain C. burnetii) provided the select agent or toxin 
has not been intentionally introduced, cultivated, collected, or 
otherwise extracted from its natural source is already excluded in 
sections 3 and 4 of the select agent regulations.
    Commenters requested that we change the statement of ``safeguarding 
of animals or plants intentionally or accidentally exposed to or 
infected with a select agent'' to read ``intentionally exposed to, or 
infected with, select agents.'' The commenters suggested that the 
statement would be clearer. We made no changes to the regulations based 
on this comment. We believe that animals or plants accidently exposed 
to or infected with a select agent should be handled as a select agent 
and safeguarded in the same manner as an animal or plant intentionally 
exposed to a select agent.
Codification of Current Practices for Shipping, Receiving and Storage
    We proposed to codify current practices for shipping, receiving, 
and storage of select agents and toxins to ensure that regulated 
entities have consistent regulatory procedures for securing and 
monitoring the shipment, receipt, and storage of these items. Some 
commenters stated that codification of current practices for shipping, 
receiving, and storage are unnecessary and recommended that the 
provision be deleted. Other commenters recommended that we define and 
clarify the term ``unexpected shipments.'' We made no changes to the 
proposed regulation based on the comments since we believe the entity's 
security plan should have documented processes to ensure select agents 
and toxins are safeguarded against theft, loss, intentional release or 
unauthorized access at all times, including when a select agent or 
toxin is (1) ready to be packaged for transportation, (2) packaged for 
shipment, or (3) received by a person with approval to access select 
agents and toxins. These procedures would serve to decrease the chance 
that such materials would be made available to an unauthorized 
individual or an individual without a legitimate use for the materials. 
We also believe that the term ``unexpected shipments'' is self-
explanatory and that an entity's security plan should contain 
procedures for the handling of unexpected shipments (e.g., when an 
entity receives a shipment of a select agent that it had neither 
requested nor coordinated for, and therefore was not expecting).
Information Security
    We proposed that the security plans of entities with select agents 
and toxins must include provisions for information security. Many 
commenters had questions or concerns regarding the additions to the 
security plan proposed in section 11(c)(9) of the select agent 
regulations. The commenters expressed concerns that the requirement 
represents an added regulatory burden and the impact of this 
requirement should be evaluated. Other commenters thought that persons 
having access to information about select agents should not be 
regulated as having access to the select agents. The commenters further 
expressed their belief that the proposed language is vague and lacks 
sufficient direction for securing the information. We agree with the 
commenters. The purpose of the requirement in question is to clarify 
section 11(c)(9)(i) of the regulation that requires the entity to have 
procedures in place for information systems control. This is an 
overarching requirement that covers electronic [information technology] 
and non-electronic [hardcopy] information

[[Page 61099]]

oversight by the regulated community. Our intent was not to regulate 
access to experimental data or the results of studies involving select 
agents and toxins but to regulate access to the select agents and 
toxins themselves. Therefore, we have revised the language in order to 
clearly indicate that the information security provisions in question 
should be for access to an entity's registered space and records 
pertaining to select agents and toxins, as identified in sections 11 
and 17 of this part.
    Commenters expressed concerns that the new information security 
requirements in section 11(c)(9)(ii) would require registration and 
security risk assessments for all staff managing records pertaining to 
select agent work. Our response is that this would depend on the 
individual's duties. If an individual is able to access a select agent 
or toxin, the individual would need to undergo a security risk 
assessment. However, if the individual's duties are limited so that he 
or she would be prevented from accessing the select agents or toxins, 
then the individual would not need to undergo a security risk 
assessment.
    We anticipate that these requirements are already being met and 
will merely require entities to document the systems and processes 
currently in place. The guidance documents developed in conjunction 
with this rule are, in part, a response to the questions and issues 
raised by the commenters. Guidance on information security may be found 
at www.selectagents.gov. Issues addressed in the guidance document 
include, but are not limited to: information technology security, 
network security, computer security, peripheral devices and data 
storage, physical security and its application to information security, 
risk management, and training.
Inventory Verification for Select Agents and Toxins
    We proposed more specific minimum security standards for select 
agents or toxins that included inventory verifications for select 
agents and toxins. Commenters requested that section 11(e)(4)(ix) be 
revised to delete the word ``all'' and clarify that the inventory 
audits be conducted for only those affected Tier 1 select agents and 
toxins. We agree with the commenters that the intent of the proposed 
provision was limited to only those select agents and toxins affected 
by the triggering event. However, we reevaluated the proposal that 
would have been limited to only Tier 1 agents and toxins, and based on 
experience, believe that this provision needs to be applied to all 
select agents and toxins. Therefore, we have revised the final 
regulatory language to address inventory verification for all select 
agents and toxins, by creating a new subparagraph (e) in section 11 
which states ``(e) Entities must conduct complete inventory audits of 
all affected select agents and toxins in long-term storage when any of 
the following occur:
    (1) Upon the physical relocation of a collection or inventory of 
select agents or toxins for those select agents or toxins in the 
collection or inventory;
    (2) Upon the departure or arrival of a principal investigator for 
those select agents and toxins under the control of that principal 
investigator; or
    (3) In the event of a theft or loss of a select agent or toxin, all 
select agents and toxins under the control of that principal 
investigator.''
Reference
    We proposed to remove the reference in Sec.  73.11(e), ``Laboratory 
Security and Emergency Response Guidance for Laboratories Working with 
Select Agents'' in Morbidity and Mortality Weekly Report (December 6, 
2002) because we posted a security guidance document in March 2007 that 
supersedes this reference. We received no comments regarding the 
removing of this reference.
Reporting Incidents to the FBI
    We proposed to add a requirement that the security plan include 
procedures for the Responsible Official to immediately notify the FBI 
of suspicious activity that may be criminal in nature and related to 
the entity, its personnel, or its select agents or toxins. Commenters 
stated that this proposal contradicts FBI guidance contained in their 
``Agricultural, Chemical and Petroleum Industry Terrorism Handbook'' 
and creates a conflict within those entities that have their own 
recognized law enforcement agencies. Commenters requested justification 
for this change and clarification on the intent of the requirement. 
Commenters also argued that the proposed language is unclear and 
unnecessary. Specifically, commenters asked what constitutes a 
``suspicious criminal activity''; what is an ``entity''; and whether 
the intent of this proposal is for the Responsible Official to be the 
designated individual to contact the FBI. We do not believe that there 
exists any conflict between the security requirements in section 73.11 
(Security) of the select agent regulations and the guidance contained 
in the FBI's ``Agricultural, Chemical and Petroleum Industrial 
Terrorism Handbook.'' However, where any conflict might exist, the 
requirements of the federal regulations would supersede guidance. The 
intent of this requirement is to facilitate the involvement of 
antiterrorism resources which will increase the security of select 
agents and toxins. We also believe that the FBI field offices, which 
are centrally located in major metropolitan areas across the United 
States, can assist the entity by working closely with them on crime 
threats. However, we agree with the commenters that it may be 
appropriate that the notification of suspicious activity first go to 
the local law enforcement. Therefore, we have changed the language in 
section 73.11(c)(8) to read: ``Describe procedures for how the 
Responsible Official will be informed of suspicious activity that may 
be criminal in nature and related to the entity, its personnel, or its 
select agents or toxins; and describe procedures for how the entity 
will notify the appropriate federal, state, or local law enforcement 
agencies of such activity.'' The guidance document on reporting 
suspicious activities may be found at www.selectagents.gov.
Intrusion Detection System
    We proposed more specific minimum security standards for select 
agents and toxins that included intrusion detection systems. Commenters 
requested clarification as to what was meant by ``intrusion detection 
system'' (IDS) and asked for examples of what constitutes an IDS. They 
also requested clarification concerning the requirement that 
``personnel monitoring the IDS must be capable of evaluating and 
interpreting the alarm.'' We have made no changes in response to this 
comment. We believe that the terms are self-explanatory and these types 
of alarms need to be monitored by personnel who are capable of 
responding appropriately. However, we are removing the words 
``prescribe and/or'' to clarify the intent of the provision. We have 
developed guidance that describes IDS as a sensor device or devices 
which triggers an alarm when a security breach occurs and notifies a 
response force (e.g., police, guards, etc.) capable of addressing any 
threat that may be present. This guidance also provides examples of 
various types of IDS. The guidance document may be found at 
www.selectagents.gov.
Submission of Security Plans
    We proposed to amend Sec.  73.11 to require that the entity 
security plan be submitted for initial registration and renewals of 
registration. Commenters recommended that we eliminate the proposed 
requirement, and stated that

[[Page 61100]]

this requirement would delay the renewal process and place entities in 
a ``regulatory bind,'' that the requirement would compromise the ``need 
to know'' status of the security plans, and that these documents should 
remain a protected document made available for review during the site 
visit only. We made no changes to the regulations based on these 
comments. Section 11 already has a provision that ``the security plan 
must be submitted upon request.'' The requirement in question merely 
codifies our long-standing policy of requesting the security plans for 
initial registration and the renewal process. We also note that, in 
practice, the submission of security plans for initial registration and 
registration renewals has not created a delay in either process.
Security for Tier 1 Select Agents and Toxins
Access Controls to Tier 1 Agents
    We proposed specific minimum security standards for access controls 
to Tier 1 agents in section 11(4)(iii) of the regulations. One 
commenter stated that these provisions would be difficult for 
laboratories co-located with other entities. We made no changes to the 
proposed standards based on this comment. Based on our experience with 
over 350 entities in a ten-year period, we observed that registered 
entities have been successful in meeting the current regulatory 
requirements in a co-located situation, and we have no reason to 
believe that this will not continue.
Back-Up Power for Tier 1 Select Agents and Toxins
    We proposed more specific minimum security standards for Tier 1 
agents that included the provision of back-up power. Commenters 
requested clarification regarding whether the back-up power requirement 
would only apply to registered spaces or whether it would include the 
entire entity or building that houses the registered space. Commenters 
recommended adding the phrase ``for the registered space'' into this 
section. We agree with the commenters and have revised the language 
accordingly.
    Another commenter stated that the provision should remain a 
recommendation not a requirement. Although we believe back-up power for 
information security networks is an essential component for the 
safeguarding of Tier 1 agents against unauthorized access, theft, loss, 
or release during power outages, further consideration led us to alter 
the nature of this requirement. Rather than focusing on power/
electricity alone, we have clarified the requirement in order to 
address the importance of having comprehensive back-up procedures in 
the event of a system failure. These procedures may include, but are 
not limited to, provisions for back-up power.
Security Enhancements for Tier 1 Select Agents and Toxins
    We proposed specific minimum security standards for Tier 1 select 
agents or toxins. Commenters requested guidance and a timetable of when 
the security upgrades need to be addressed. In this final rule, we have 
included a phase-in period for the effective date for certain 
requirements which should allow entities sufficient time to comply 
without causing disruption or termination of research or educational 
projects. As noted in the ``Effective Dates'' portion of this document, 
one hundred and eighty days after the publication of the final rule, 
entities will need to be in compliance with new provisions outlined in 
section 11 (Security). In addition, we have developed guidance to 
assist entities with security enhancements for Tier 1 agents.
    Other commenters stated that the proposed rule included more 
specific minimum security standards for Tier 1 select agents and toxins 
and requested that we identify criteria for stratifying security 
requirements, making them risk-based and considering the type of work 
performed at the facility. The commenters also argued that the 
additional regulations for Tier 1 agents and toxins will create more 
responsibilities for the entity and require more resources to meet 
these requirements. While we are in general agreement with these 
concerns, we note that entities possessing Tier 1 agents and toxins are 
already meeting these requirements. In addition, we have developed 
guidance to assist entities with security enhancements for Tier 1 
agents, which may be found at www.selectagents.gov. Therefore, we are 
making no changes to the minimum security standards as proposed in the 
NPRM.
Suitability Assessment for Access to Tier 1 Select Agents and Toxins
    We proposed specific minimum security standards, including 
personnel suitability assessments, for access to Tier 1 select agents 
and toxins. Many commenters had questions or concerns regarding these 
additional requirements, as described in section 11(f) of the proposed 
rule. Specific additions addressed by the commenters included: Pre-
access suitability assessments, ongoing suitability assessments, and 
self- and peer-reporting of incidents or conditions that could affect 
an individual's ability to safely have access to or work with Tier 1 
select agents and toxins. Commenters generally divided into two groups 
in their response to the proposed additions. Some felt that the 
requirements were too vague to prove useful and the requirements 
created administrative burden without improving the overall security of 
Tier 1 select agents and toxins. Others felt that the requirements 
could or would require entities to behave in a manner contrary to local 
laws, privacy laws, or union contracts. Commenters also felt that the 
proposed language, ``individuals with access approval to select agents 
and toxins are trustworthy and behaving in a manner that upholds public 
health and safety, security, and the integrity of the scientific 
enterprise'' were subjective standards that would be difficult to 
enforce. We agreed with the commenters and revised the language in the 
final rule to read that the security plan must contain procedures that 
will limit access to a Tier 1 select agent or toxin to only those 
individuals who are approved by the HHS Secretary or Administrator, 
following a security risk assessment by the Attorney General, have had 
an entity-conducted pre-access suitability assessment, and are subject 
to the entity's procedures for ongoing suitability assessment.
    We anticipate that these requirements are already being met at many 
registered entities and will merely require those entities possessing a 
Tier 1 select agent or toxin to formalize and document the systems and 
processes currently in place. Therefore, we do not believe the 
registered entities possessing a Tier 1 select agent or toxin will 
endure additional significant costs for suitability assessments. We 
believe that many of the specific concerns raised by commenters 
regarding potential violation of laws or union contracts arose as a 
result of the commenters' examination of the FESAP November 2, 2010 
document entitled ``Recommendations Concerning the Select Agent 
Program.'' As a matter of clarification, the Federal Select Agent 
Program considered the FESAP recommendations as well as recommendations 
from other sources (e.g., the National Science Advisory Board for 
Biosecurity, the National Research Council, and the EO 13486 Working 
Group), in developing the proposed rule provisions addressing personnel 
suitability. While we have created specific guidance regarding this

[[Page 61101]]

section of the revised rule, we are leaving the regulations in their 
broadly-written state in order to provide entities with flexibility in 
meeting these requirements. Given our experience with the select agent 
regulations and the wide variety of regulated entities those 
regulations cover, we have found this to be the most effective 
approach. The personnel suitability guidance document developed in 
conjunction with this rule is, in part, a response to the questions and 
issues raised by the commenters. Issues addressed in the guidance 
document include, but are not limited to:
    (1) Understanding the potential for insider threat;
    (2) Understanding the needs for suitability assessments;
    (3) Delineating the roles and responsibilities of individuals to 
ensure optimal security;
    (4) Requesting information about individuals in a standardized 
manner and assessing individuals in the context of safety and security;
    (5) Responding to reports in a consistent, prompt, and confidential 
manner;
    (6) Providing training for recognizing and reporting suspicious 
behavior.
    Full guidance on suitability assessments may be found at 
www.selectagents.gov.
    One commenter requested an exclusion or exemption clause for 
entities that are registered to possess Tier 1 select agents or toxins, 
but do not possess them. We made no changes to the regulations based on 
this comment. Entities that are registered to possess, use or transfer 
select agents and toxins must meet all of the regulatory requirements, 
regardless of whether or not they actually possess these materials.
Security Training for Access to Tier 1 Select Agents and Toxins
    We proposed specific minimum security standards, including security 
training, for those individuals who would have access to Tier 1 select 
agents or toxins. Commenters requested clarification whether training 
of ``all entity employees'' mentioned in section 11(e)(2)(ii) meant 
everyone in the facility or those ``Security Risk Assessment-approved 
employees.'' We agree with the commenters and have revised the language 
in the regulations to clarify that the training is for employees with 
access to Tier 1 select agents and toxins.
Three Barriers for Tier 1 Select Agents and Toxins
    We proposed specific minimum physical security standards for Tier 1 
select agents or toxins that included a requirement for three barriers 
protecting access to these materials. Commenters requested 
clarification regarding what was meant by ``barrier'' and asked for 
examples of what constitutes as a barrier. They also requested 
clarification concerning the word ``delay'' since, according to the 
commenters, the word does not seem to describe the needed function.
    We agree with the commenters that the word barrier needed further 
explanation and, in the definitions section in Sec.  73.1, we have 
defined the term ``Security barrier'' as a physical structure that is 
designed to prevent entry by unauthorized persons. In addition, we have 
revised the language in this section to more clearly articulate that 
entities possessing Tier 1 select agents and toxins must have a minimum 
of three security barriers where each security barrier adds to the 
delay in reaching secured areas where select agents and toxins are used 
or stored. One of those security barriers must be monitored in such a 
way as to detect intentional and unintentional circumventing of 
established access control measures under all conditions (day/night, 
severe weather, etc.). The final barrier must limit access to the 
select agent or toxin to personnel approved by the HHS Secretary or 
Administrator, following a security risk assessment by the Attorney 
General.
    Other commenters believed that the proposed requirement represents 
an added expense. Although we agree that there are expenses associated 
with the implementation of security measures, we do not anticipate that 
significant additional expenditures will be necessary for registered 
entities already possessing Tier 1 select agents or toxins. We have 
developed guidance to assist entities with the security barrier 
requirement, which may be found at www.selectagents.gov.
Response Time for Tier 1 Select Agents and Toxins
    We proposed specific minimum security standards, including a 
response time for security forces or local police that could not exceed 
15 minutes from the time of an intrusion alarm or report of a security 
incident in section 73.11(e)(4)(viii), for possessors of Tier 1 select 
agents and toxins. Commenters questioned why a 15 minute response time 
was chosen. Commenters also inquired whether there would be any 
penalties if local law enforcement exceeds 15 minutes with their 
response time. In addition, commenters stated that the proposed 
definition of response time is unclear. One commenter recommended that 
we revise the provision to read ``Response time for security forces or 
local police must not exceed 15 minutes from the time of alerting the 
designated force.''
    Based on the comments received, we have modified the language of 
this section. While retaining a 15-minute response time goal for 
security forces or local police, we have provided flexibility for 
entities to develop systems in line with the optimal achievable 
response time in their area by revising the language to read: ``The 
entity must: (A) Determine that the response time for security forces 
or local police will not exceed 15 minutes or (B) Provide security 
barriers that are sufficient to delay unauthorized access until the 
response force arrives in order to safeguard the select agents and 
toxins from theft, intentional release, or unauthorized access. The 
response time is measured from the time of an intrusion alarm, or 
report of a security incident, to the arrival of the responders at the 
first security barrier.''
    Our selection of the 15 minute response time metric is based on DOD 
and DHS standards for high value assets (e.g., MD Number 11046 (Open 
Storage Area Standards for Collateral Classified Information), 
Department of Homeland Security Management Directive System MD) and 
also on our analysis of incident response plans provided by registered 
entities since 2003. The response time is measured from the time of an 
intrusion alarm, or report of a security incident, to the arrival of 
the responders at the first security barrier. A response is a force 
capable of interrupting a threat and may be unarmed guards, armed 
guards, or local law enforcement.
Security Requirements for Variola Major Virus or Variola Minor Virus
    In recognition of the special public health risks associated with 
Variola major virus and Variola minor virus, we proposed to require 
additional physical security measures over and above those proposed for 
Tier 1. Commenters were concerned about listing the Variola major virus 
(smallpox virus) as a Tier 1 agent, given the stringent conditions 
already in place for its handling and tracking. The commenters 
recommended an alternative approach might be to designate the smallpox 
virus as a pathogen with very special handling requirements, given that 
smallpox has been officially eradicated worldwide.

[[Page 61102]]

    We made no changes to the regulations based on the comment. We 
believe that setting up a different special class of standards for one 
pathogen would needlessly increase the complexity of the regulatory 
provisions without any benefit of increased security. The requirements 
designated for Tier 1 agents were meant for those select agents and 
toxins that present the greatest risk of deliberate misuse with the 
most significant potential for mass casualties or devastating effects 
to the economy, critical infrastructure, or public confidence. As such, 
Variola major virus and Variola minor virus meet that criterion. We 
also note that Variola major virus is a special case and that there are 
additional, specific requirements for Variola major virus in addition 
to the Tier 1 requirements. These specific requirements for Variola 
major virus and Variola minor virus do not apply to the other Tier 1 
agents.
    One commenter requested clarification that requirements are not 
applicable to diagnostic laboratories that may identify Variola major 
virus or Variola minor virus during the course of routine work, but 
would not otherwise ``possess'' these agents. We made no changes to the 
regulations based on this comment. We note that the clinical and 
diagnostic laboratory exemption found in section 5 of the regulations, 
including all of the reporting and safeguarding requirements, remains 
in effect.
    Since the publication of the proposed rule, we became concerned 
that the proposed requirement for all persons with access to the 
Variola major or Variola minor virus to have a Top Secret clearance 
would have the unintended effect of preventing HHS/CDC researchers from 
being able to participate in collaborative work with international 
colleagues, such as representative of the World Health Organization. To 
address this concern, we have decided to modify the requirement to 
require only personnel with independent unescorted access to Variola 
major or Variola minor virus to have a Top Secret security clearance. 
The requirements that any access to Variola major or Variola minor 
would require approval from HHS/CDC and the approval of the Federal 
Select Agent Program would remain in effect.
Biosafety Plan
    One commenter was concerned that specifying the ``Biosafety in 
Microbiological and Biomedical Laboratories'' (BMBL) (Ref 28) 
publication in the regulatory text would in effect incorporate the 
document by reference and therefore the BMBL should be published in the 
Federal Register for public comment. We made no changes to the 
regulations based on this comment. The BMBL has not been incorporated 
by reference. The regulation clearly states that an individual or 
entity should ``consider'' the BMBL when developing a site specific 
biosafety plan. The BMBL is listed in the regulations because it 
provides useful guidance for how to work safely with a variety of 
pathogens. It also describes standard and special microbiological 
practices, safety equipment, and facilities (constituting Biosafety 
Levels 1-4). It is the document that is generally recognized as the 
national biosafety standard in the United States.
    Another commenter recommended that we clarify features of 
containment infrastructure intended to facilitate biosafety of workers 
dealing with these materials. The commenter recommended the regulatory 
language read ``The biosafety plan must contain sufficient information 
and documentation to describe the biosafety, physical and operational 
containment requirements for working with the select agent or toxin 
including any animals or plants intentionally or accidentally exposed 
to or infected with a select agent.'' We made no changes to the 
regulations based on this comment since we believe the proposed 
language is clear and sufficient.
    Another commenter recommended we remove the statement: ``The 
occupational health program may also be made available to individuals 
without access to Tier 1 select agents and toxins.'' We agree with the 
commenter and have eliminated that portion of the regulatory text.
Occupational Health Program
    We also proposed that the biosafety plan must include provisions 
for the implementation of an occupational health program for 
individuals with access to Tier 1 select agents and toxins. Many 
commenters had questions and/or concerns regarding the addition of a 
requirement for an occupational health program. Commenters generally 
divided into two categories in their comments. Some commenters felt 
that the requirement was too vague to prove useful and that the 
requirement created an administrative burden without improving the 
overall biosafety of Tier 1 select agents and toxins. Other commenters 
indicated that the requirement could or would require entities to 
behave in a manner contrary to Health Insurance Portability and 
Accountability Act of 1996 (HIPAA). Commenters also felt that a 
preventive health and post-exposure program is already available at 
registered entities and should not be a requirement in the regulations. 
We made no changes based on these comments.
    While the select agent regulations do not supersede HIPAA, HIPAA 
does not prevent the requirement of the establishment of an 
occupational health program to address biosafety concerns for those 
handling select agents and toxins.
    We anticipate that this requirement is already being met and will 
merely require those entities possessing a Tier 1 select agent or toxin 
to codify and document the systems and processes currently in place. 
Therefore, we do not believe registered entities possessing a Tier 1 
select agent or toxin will endure significant additional costs 
associated with an occupational health program. While we have created 
specific guidance regarding this section, we are leaving the specifics 
of the occupational health program as performance-based standards in 
order to provide entities with flexibility in meeting these 
requirements. We have found this to be the most effective approach 
given the wide variety of regulated entities these regulations cover. 
Full guidance on an occupational health program may be found at 
www.selectagents.gov.
Restricted Experiments
    We proposed to add language in order to expand the ``restricted 
experiment'' approval requirement to include all experiments involving 
the creation of drug resistant select agents that are not known to 
acquire that resistance naturally, if such acquisition could compromise 
the control of disease agents in humans, veterinary medicine, or 
agriculture regardless of the method or technology used to create the 
resistance. Previously, the restricted experiment language concerned 
only those experiments involving recombinant nucleic acids.
    The restricted experiment definition currently covers the 
``deliberate transfer of a drug resistance trait to select agents that 
are not known to acquire the trait naturally, if such acquisition could 
compromise the use of the drug to control disease agents in humans, 
veterinary medicine or agriculture.'' We have removed the phrase ``use 
of the drug'' and modified the language in the last sentence to read 
``deliberate transfer of a drug resistance trait to select agents that 
are not known to acquire the trait naturally, if such acquisition could 
compromise the control of disease agents in humans, veterinary medicine 
or agriculture.'' We made this change because while the introduction of 
a drug resistance trait would normally

[[Page 61103]]

eliminate that drug as a therapeutic option to control the disease, 
there may be alternative drugs available to control the disease. 
Therefore, the new definition reads as follows: Restricted experiments 
are defined as: ``(1) experiments that involve the deliberate transfer 
of, or selection for, a drug resistance trait to select agents that are 
not known to acquire the trait naturally, if such acquisition could 
compromise the control of disease agents in humans, veterinary 
medicine, or agriculture;'' and ``(2) experiments involving the 
deliberate formation of synthetic or recombinant nucleic acids 
containing genes for the biosynthesis of select toxins lethal for 
vertebrates at an LD[50] < 100 ng/kg body weight.''
    It should be noted that restricted experiments are not prohibited 
experiments. However, an entity must seek permission prior to the 
initiation of a restricted experiment and receive approval from the 
Administrator or HHS Secretary. Approval for the performance of a 
restricted experiment or the possession of a product of a restricted 
experiment may involve meeting additional safety and/or security 
requirements as prescribed by the Federal Select Agent Program. Many 
experiments that involve the deliberate transfer of a drug resistant 
trait do not meet the definition of a restricted experiment because the 
drug is not used to control disease in humans, veterinary medicine, or 
agriculture. The Federal Select Agent Program encourages anyone who 
intends to conduct a select agent experiment utilizing drug resistance 
markers to submit that experiment for review so that they can be 
advised on whether the experiment would be considered a restricted 
experiment and require approval prior to its initiation.
    One commenter stated that ``denial of restricted experiments is an 
obstacle to the development of countermeasures instead of promoting 
real biosecurity.'' We made no changes based on this comment. As 
mentioned previously, many experiments that involve the deliberate 
transfer of a drug resistant trait to a select agent do not meet the 
definition of a restricted experiment because the drug is not used to 
control disease in humans, veterinary medicine, or agriculture. The 
rationale for requiring a heightened review of experiments that involve 
introduction of a drug resistant trait to a select agent for 
therapeutically useful antibiotics is ultimately out of concern that 
what is made in the laboratory might not always remain in the 
laboratory and therefore present a public health or agricultural risk. 
For experimental protocols utilizing transient drug resistant traits, 
it should be noted that mutants possessing those traits can be 
maintained without removal of the trait and therefore pose a potential 
risk to public health or agriculture. We therefore consider these 
protocols to fall under the restricted experiment section of the 
regulations.
    Commenters also suggested aligning the restricted experiment 
language with the ``NIH Guidelines for Research Involving Recombinant 
DNA Molecules'' (NIH Guidelines) language that restricts and requires 
approval for experiments with pathogens involving drug resistance for 
therapeutically useful agents against that pathogen. We made no changes 
based on these comments. The definition of a restricted experiment is 
aligned with the NIH Guidelines and reads as ``* * * select agents that 
are not known to acquire the resistance naturally, if such acquisition 
could compromise the control of disease agents in humans, veterinary 
medicine, or agriculture.'' We have not expanded the definition to 
include the introduction of all drug resistant traits to a select agent 
but only to those traits used to control disease in humans, veterinary 
medicine, or agriculture.
Incident Response
    One commenter argued that since the incident response plan must 
fully describe the entity's response policies or procedures for failure 
of intrusion detection or alarm system, the Federal Select Agent 
Program should provide clarification as to what was meant by an 
intrusion detection system (IDS) and examples of what constitutes IDS. 
We have developed guidance that describes IDS as a sensor device or 
devices which triggers an alarm when a security breach occurs and 
notifies a response force (e.g., police, guards, etc.) capable of 
addressing any threat that may be present. This guidance also provides 
examples of various types of IDS. The guidance document may be found at 
www.selectagents.gov.
    One commenter recommended that instead of using the word ``etc.'' 
in section 14(b) they recommended that the section state, ``* * * and 
emergencies such as fire, gas leak, explosion, power outage, and other 
natural and man-made events.'' We agreed with the commenter and revised 
the language.
    While we did not propose any changes to section 73.14 (c)(6), a 
commenter recommended that the language regarding planning and 
coordination with local emergency responders be amended. Specifically, 
the commenter believed that biosafety, as opposed to biosecurity needs, 
would be better addressed if this provision read as follows: ``* * * 
emergency responders, including local public health authorities.'' We 
made no changes to the section based on the comment since the proposed 
language would limit the concept to only public health authorities and 
not agricultural health. Emergency responders can also include police, 
fire and rescue service, and emergency medical service.
Training
    We proposed to specify that the Responsible Official ensure 
maintenance of training records since there was no particular person 
designated as the entity's required record keeper, only that a training 
record must be kept. We received no comments regarding this proposal.
    We proposed to amend the regulations in 42 CFR 73.15 that contain 
provisions of mandatory training for staff and visitors who work in or 
visit areas where select agents or toxins are handled or stored to 
provide security awareness and incident response training. Commenters 
requested clarification concerning the required annual insider threat 
awareness briefings for those entities possessing a Tier 1 select agent 
or toxin as proposed in section 15(b) of the select agent regulations. 
The commenters asked that the content of these threat awareness 
briefings be made available to public health laboratories so that it 
could then be specifically customized for various regions of the 
country and include what are the minimum requirements, who the intended 
audience is, and what documentation will be needed to satisfy the 
requirement.
    While we have created specific guidance regarding this section of 
the revised regulations, the guidance does not take the form of a 
prescriptive program. Given our experience with the select agent 
regulations and the wide variety of entities those regulations cover, 
we have found a broader approach to be most effective. The guidance 
documents developed in conjunction with this rule are, in part, a 
response to the questions and issues raised by the commenters. The 
document regarding annual insider threat awareness briefings includes a 
designated person to manage the assessment of laboratory personnel, 
laboratorian involvement in threat mitigation, and behaviors of concern 
as specific examples of best practices that we believe entities would 
be well served in adopting. Full guidance on this and other issues may 
be found at www.selectagents.gov.

[[Page 61104]]

    One commenter proposed that the requirements for incident response 
training should remain as currently written to only include safety 
incident training via annual blood-borne pathogens, general safety, 
biological hygiene, chemical hygiene, and lab specific select agent 
training. We made no changes to the proposed requirement based on this 
comment because we believe that incident response training needs to be 
expanded so that personnel are trained in how to safeguard select 
agents and toxins during natural emergencies and man-made disasters.
    Commenters requested clarification that refresher training would 
only be mandated when substantive changes are made to the plans 
including what level of retraining would be required and whether 
retraining would only be required for those areas of the plan that have 
been amended. We made no changes to the proposed requirements based on 
these comments. We believe that the regulatory language clearly states 
that training will need to be provided when significant processes are 
changed in the plan and that training will need to be provided to those 
individuals who are affected by these changes in the plan.
    One commenter recommended that we consider the staff time it will 
take for visitor training. We made no changes to the proposed 
requirement based on this comment. First, we believe that it is very 
important that visitors receive the appropriate incidence response and 
security awareness training to protect their personal safety while in 
registered areas. We do not believe that the staff time needed to 
fulfill this requirement will cause a significant increase in time and 
effort when integrated into the current visitor training program.
    One commenter requested clarification on the refresher training of 
escorted personnel and visitors because the commenter believed that 
refresher training is only required once a year, but does not happen 
with visitors or escorted personnel. We agreed with the commenter and 
have revised the language to read: ``Refresher training must be 
provided annually for individuals with access approval from the HHS 
Secretary or Administrator or at such time as the registered individual 
or entity significantly amends its security, incident response, or 
biosafety plans.''
Transfers
    We proposed to clarify when ``transportation in commerce'' begins 
and ends to better allow registered entities to adequately address 
those situations when a select agent or toxin is (1) ready to be 
packaged for transportation, (2) packaged for shipment, or (3) received 
and handled by a person with approval to access select agents and 
toxins. One commenter stated that the security of the package between 
steps (2) packaged for shipment and (3) received and handled by a 
person with approval to access select agents and toxins should be the 
sole responsibility of the courier. We made no changes to the language 
based on this comment. As stated in the preamble to the proposed rule, 
``transportation in commerce'' begins when the select agent(s) or 
toxin(s) are packaged for shipment and ready for receipt by a courier 
and ends when the package is received by the intended recipient who is 
an individual approved by the HHS Secretary or Administrator to have 
access to select agents and toxins, following a security risk 
assessment by the Attorney General.
    Commenters believed that the new provision outlined in section 
16(f) meant that all transfers must be made by an individual approved 
by the HHS Secretary or Administrator to have access to select agents 
and toxins, following a security risk assessment by the Attorney 
General. We agreed with the commenters and revised the language to 
state that after authorization is provided by USDA/APHIS or HHS/CDC, 
the packaging of the select agent(s) and toxin(s) is performed by an 
individual approved by the HHS Secretary or Administrator to have 
access to select agents and toxins and is in compliance with all 
applicable laws concerning packaging.
Records
    We proposed to clarify the current language that an accurate, 
current inventory needs to be maintained for each select agent that the 
entity possesses including synthetic select agent organisms and any 
animals or plants intentionally or unintentionally exposed to or 
infected with a select agent (including number and species, location, 
and appropriate disposition). Commenters argued that counting 
individual vials of replicating biological agents is costly, 
burdensome, and a major source of frustration for investigators. They 
further claimed that there is widespread concern that both counting 
vials and measuring volumes of individual vials are not effective means 
of increasing security and wondered if there was another way to account 
for inventory. Other commenters noted that animals infected with a 
select agent are part of ongoing experimentation and are thus part of 
working stocks rather than current inventory and requested 
clarification on whether or not the term ``animal'' also included 
``arthropods.''
    We are making no changes to the regulations based on these 
comments. While we are aware of the burden resulting from the 
requirement to maintain an accurate and current inventory of each 
select agent and toxin held in long-term storage, we believe this is an 
essential element to establish security of select agents or toxins. We 
recognize that it may still be possible for an insider to steal a 
sample of an agent either from working stock or from an inventory 
without being detected. However, if an entity has a robust inventory 
management system, such incidents have a better chance of being 
detected. To assist registered entities in meeting the requirements for 
accurate inventories of materials in long term storage, we have 
developed guidance that may be found at www.selectagents.gov.
    It should be noted that while the volume measurements the commenter 
references are required for inventories of select toxins, they are not 
required in the case of inventory of select agents held in long-term 
storage due, in part, to the points raised by the commenter. However, 
we disagree with the commenter's assessment that measuring volume in 
the case of select toxins and counting vials in general, as part of 
required inventory tracking of both select agents and toxins for 
registered entities, is not necessary.
    We recognize that there has been some confusion between those 
infected animals (including arthropods) and plants considered to be 
``working stock'' and those considered to be ``inventory held in long 
term storage.'' To that end, we have developed specific guidance that 
will enable entities to better differentiate between these two 
categories. This guidance is available at www.selectagents.gov.
    In order to clarify our intent regarding ``working stock'' and 
``inventory held in long term storage,'' as it relates to infected 
animals and plants, we are revising paragraph (a)(2) in section 17 of 
the select agent regulations to require an accurate, current accounting 
of any animals or plants intentionally or accidentally exposed to or 
infected with a select agent (including number and species, location, 
and appropriate disposition) instead of an accurate, current inventory 
of those animals or plants.
    One commenter had concerns about tracking nucleic acids for 
laboratories, which generate bacterial mutants and perform reverse 
genetics. The commenter believed that this would be

[[Page 61105]]

incredibly time consuming, overly burdensome, and of no value. The 
commenter argued that the theft of viral genetic elements would be less 
useful to a person without scientific expertise and unnecessary for the 
individual with the skills.
    We made no changes to the regulations based on this comment. It 
should be noted that not all recombinant material is regulated. The 
scenarios described by this commenter would not involve regulated 
nucleic acids. For example, bacterial genomes and viral genomes not 
determined to be infectious are not subject to these regulations. 
Additional guidance on this topic is available at www.selectagents.gov.
Administrative Review
    We proposed to amend the regulations in 42 CFR 73.20 that addresses 
the administrative review of an individual or entity's denial, 
revocation, or suspension of registration or access approval. 
Specifically, we proposed to modify the current regulations in order to 
allow individuals more time to gather the necessary components of their 
appeal following the denial, limitation, or revocation of access 
approval. In addition, we proposed to remove the provision ``Where the 
denial, revocation, or suspension of an individual's access approval is 
based upon identification by the Attorney General, the request for 
review will be forwarded to the Attorney General'' to provide 
clarification that the decision regarding the appeal is determined by 
the HHS Secretary. We received comments supporting these proposed 
changes.
Guidance Documents
    In the proposed rule, we specifically requested comment from the 
regulated community and any other interested persons on the need for 
and desirability of guidance documents that would serve to assist 
regulated entities in meeting the requirements of regulations. We were 
particularly interested in public comment regarding Web sites, 
articles, or other sources that may be useful in developing such 
guidance documents. We received a number of comments on the issue of 
guidance which are discussed below. As these comments pertain to the 
development of guidance documents and not to the regulations 
themselves, we have made no regulatory changes as a result. Guidance 
documents may be found at www.selectagents.gov.
    Commenters stated that further sources of information, apart from 
interaction with Federal Select Agent Program inspectors, should be 
made available to assist regulated entities in implementing the 
additional requirements. Other commenters urged that we develop 
guidance as a collaborative effort with a variety of subject matter 
experts both inside and outside the government.
    We agreed with these comments and consulted with a wide variety of 
contributors including HHS and USDA subject matter experts, a National 
Science Advisory Board for Biosecurity report entitled ``Enhancing 
Personnel Reliability among Individuals with Access to Select Agents'' 
(Ref 24), the National Academies Committee on Laboratory Security and 
Personnel Reliability Assurance Systems for Laboratories Conducting 
Research on Biological Select Agents and Toxins report entitled 
``Responsible Research with Biological Select Agents and Toxins'' (Ref 
25), the Report from the Executive Order 13486 Working Group on 
Strengthening Laboratory Security in the United States (Ref 26), and a 
report from the Defense Science Board Task Force on Department of 
Defense Biological Safety and Security Program (Ref 27).
    There exist a variety of ways for regulated entities to obtain 
information from the Federal Select Agent Program. HHS/CDC and USDA/
APHIS may be contacted via email at lrsat@cdc.gov 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 use of the term ``biosafety'' in 42 CFR 73.12 as compared to 
the term ``biocontainment'' found in USDA/APHIS's regulations in 7 CFR 
331.12.
    Since the Federal Select Agent Program is jointly administered by 
USDA/APHIS and HHS/CDC, we make every effort to achieve congruence 
between our various regulations. In certain cases, as a result of the 
differences between plant, animal and human select agents and toxins, 
the terminology employed must necessarily differ. The term 
``biocontainment'' is found in the USDA/APHIS regulations in 7 CFR 
331.12 relating to Plant Protection and Quarantine (PPQ) select agents 
and toxins while the term ``biosafety'' is found in the USDA/APHIS 
regulations in 9 CFR 121.12 relating to Veterinary Services (VS) select 
agents and toxins. ``Biosafety'' is the accurate term to describe 
procedures relating to humans or animals. However, the term 
``biocontainment'' is more appropriate for describing procedures 
necessary to contain plant pathogens.
Animals or Plants Exposed to or Infected With Select Agents or Toxins
    We proposed to require that security, biosafety, and incident 
response plans include provisions to address the safeguarding of 
animals or plants accidentally or intentionally exposed to or infected 
with select agents against unauthorized access, theft, loss or release. 
Commenters requested clarification about whether this requirement would 
be limited to experimental plants and animals that are possessed by and 
controlled by the registered entity. We made no changes to the 
requirement based on these comments. An entity's security, biosafety, 
and incident response plans should address any plants or animals within 
the entity that may be exposed to a select agent, regardless of whether 
or not the exposure was intentional or accidental.
    Another commenter requested clarification on whether the term 
``animal'' included arthropods. We made no changes based on this 
comment as the term ``animal'' does include arthropods.
Cost
    Commenters requested that we consider the indirect consequences of 
continuing to include agents and toxins on the select agent list, the 
negative effect of the proposed rule changes on the potential workforce 
for select agent research, and the possibility that additional 
regulations concerning Tier 1 select agents and toxins will mandate 
more federal oversight and institutional

[[Page 61106]]

compliance requirements, resulting in increased costs to taxpayers both 
directly and indirectly through reduced research efficiency. Commenters 
requested that a full financial and scientific impact of these added 
requirements be carefully assessed prior to implementation, especially 
the increased costs to academic institutions with no associated 
funding, and the increased burden on investigators already having 
difficulty finding time for research and experimentation. The 
commenters also stated that the timeline for implementation of the new 
requirements should be considered and disclosed to affected entities.
    A cornerstone of the Federal Select Agent Program is to establish 
and enforce safety and security measures to prevent access to select 
agents and toxins for use in domestic or international terrorism or for 
any other criminal purpose. An equally important function of the 
Federal Select Agent Program is to allow for the appropriate 
availability of biological agents and toxins for research, education, 
and other legitimate purposes. To achieve both requires the balancing 
of the need for continuing biological research with requiring a level 
of safety and security commensurate with the risks posed by these 
biological agents and toxins. We understand that safety and security 
requirements cost money and that money in the area of biological 
research is often a scarce commodity. However, we are also aware that a 
lack of adequate safety and security requirements could result in 
damages measured both in dollars and in human lives. It is our 
determination, based on the information available to us, that the 
additional requirements would not constitute a significant economic or 
recordkeeping burden on the regulated entities. We also believe that in 
many cases these regulations serve to codify systems and procedures 
already in use by a majority of regulated entities.
    To achieve regulatory flexibility, we have included a phase-in 
period for the effective date for certain requirements of the revised 
regulations which should allow entities to comply without causing 
disruption or termination of research or educational projects. As noted 
in the ``Effective Dates'' portion of this document, sixty (60) days 
from the publication of the final rule, entities will need to be in 
compliance with sections 1-10, 13, 16, and 20. One hundred and eighty 
days after the publication of the final rule, entities will need to be 
in compliance with sections 11 (Security), 12 (Biosafety), 14 (Incident 
response), and 15 (Training).
Request for a Letter of Interpretation Policy
    One commenter suggested that the Federal Select Agent Program 
should augment guidance documents with a letter of interpretation 
policy. Specifically, the commenter recommended that select agent 
registrants should be able to submit written requests detailing a 
compliance issue and receive back a written letter of interpretation 
from the Federal Select Agent Program in a similar manner as employers 
can submit requests for interpretation to the Department of Labor 
Occupational Safety and Health Administration. We are making no changes 
to the select agent regulations based on this comment because it is 
outside the scope of this rule.

III. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    Executive Orders 12866 and 13563 direct agencies to assess all 
costs and benefits of available regulatory alternatives and, if 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety effects, distributive impacts, and equity). Executive 
Order 13563 emphasizes the importance of quantifying both costs and 
benefits, of reducing costs, of harmonizing rules, and of promoting 
flexibility.
    Under Executive Order 12866, HHS must determine whether a 
regulatory action is ``significant.'' A ``significant regulatory 
action'' under Executive Order 12866 is defined as (1) an action that 
is likely to result in a rule that may have an annual effect on the 
economy of $100 million or more, or adversely and materially affects a 
sector of the economy, productivity, competition, jobs, the 
environment, public health or safety, or state, local or tribal 
governments or communities (or an economically significant action); (2) 
creates a serious inconsistency or otherwise interferes with an action 
taken or planned by another agency; (3) materially alters the budgetary 
impact of entitlements, grants, user fees or loan programs or the 
rights and obligations of recipients; or (4) raises novel legal or 
policy issues. Because this rulemaking proposes changes to how a subset 
of select agents and toxins is protected, this rule has been determined 
to be ``significant'' under Executive Order 12866 and, therefore, has 
been reviewed by the Office of Management and Budget (OMB).
    We have prepared an economic analysis for this rule. The economic 
analysis provides a cost-benefit analysis, as required by Executive 
Order 12866, and a final regulatory flexibility analysis (See Section 
III.B. of this Preamble) that examines the potential economic effects 
of this rule on small entities, as required by the Regulatory 
Flexibility Act. The economic analysis is summarized below. Copies of 
the full analysis are available on www.regulations.gov, Docket CDC-
2012-0012, at www.select agents.gov or by contacting the person listed 
under FOR FURTHER INFORMATION CONTACT.
Summary of the Regulatory Impact Analysis
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 (Pub. L. 107-188) provides for the regulation of 
certain biological agents and toxins that have the potential to pose a 
severe threat to human, animal, or plant health, or to animal or plant 
products. The Animal and Plant Health Inspection Service (APHIS) and 
the Centers for Disease Control and Prevention (CDC) have primary 
responsibility for implementing the provisions of the Act within the 
Department of Agriculture and the Department of Health and Human 
Services, respectively. Within APHIS, Veterinary Services (VS) select 
agents and toxins are those that have been determined to have the 
potential to pose a severe threat to animal health or animal products, 
and Plant Protection and Quarantine (PPQ) select agents and toxins are 
those that have been determined to have the potential to pose a severe 
threat to plant health or plant products. HHS select agents and toxins 
are those that have been determined to have the potential to pose a 
severe threat to human health. USDA/APHIS and HHS/CDC coordinate 
regulatory activities for overlap select agents and toxins that have 
been determined to pose a severe threat to human and animal health or 
animal products.
    Sections 201 and 212(a)(2) of the Act require a biennial review and 
republication of the select agent and toxin list, with revisions as 
appropriate in accordance with this law. These final rules will 
implement the recommendations of the third biennial review, and 
incorporate risk-based tiering of the select agent and toxin lists, as 
required by Executive Order 13546, ``Optimizing the Security of 
Biological Select Agents and Toxins in the United States.'' In 
addition, the APHIS and CDC final rules will codify several amendments 
to the regulations, including the addition of definitions and 
clarification of language concerning security, training, biosafety/

[[Page 61107]]

biocontainment, and incident response. These changes will improve the 
applicability and effectiveness of the select agent regulations and 
provide for enhanced program oversight.
    Based on information obtained through site-specific inspections, we 
believe most registered entities already have in place many of the 
information security requirements set forth in the final rules, and 
compliance costs of the rules are therefore expected to be minimal. 
Entities more likely to be affected will be laboratories and other 
institutions conducting research and related activities that involve 
the use of select agents and toxins categorized as Tier 1. These 
entities will be required to conduct a pre-access suitability 
assessment of individuals with access to a Tier 1 select agent or 
toxin, as well as enroll these individuals in an occupational health 
program.
    The rules would reduce the period that FBI background checks are 
valid from five to three years. This increased frequency would 
effectively increase the cost of background checks by 67 percent. Based 
on the current number of individuals required to have the background 
checks, we estimate that the present value of these government-borne 
costs over five years will increase by $1.96 million across all 
registered entities. The annual increase in costs will total about 
$432,000.
    While we expect few if any of the registered entities to incur 
significant compliance costs, required documentation of measures 
already regularly performed with respect to biocontainment/biosafety, 
incident response, information security, and ongoing suitability 
assessment may require additional time of personnel. We estimate 
additional recurring costs related to information security, such as for 
software updates, could total about $2 million per year, or about 
$5,500 per entity, in the unlikely event that none of the entities 
already uses equivalent information security measures. As noted, many 
of these costs are already currently borne by entities in their conduct 
of generally recognized best practices. For entities possessing a Tier 
1 agent or toxin, the costs of pre-access suitability assessments and 
occupational health programs are estimated to total between $2.8 
million and $4.4 million, or between about $9,600 and $15,100 per 
entity, on average. Again, actual costs incurred are unlikely to reach 
these maximum cost ranges; we expect that many of the entities with a 
Tier 1 agent or toxin already conduct assessments and have health 
programs similar or equivalent to those required by the final rules.
    The benefits of strengthened safeguards against the unintentional 
or deliberate release of a select agent or toxin greatly exceed 
compliance costs of the rules. As an example of losses that can occur, 
the October 2001 anthrax attacks caused 5 fatalities and 17 illnesses, 
disrupted business and government activities (including $2 billion in 
lost revenues for the Postal Service), and required more than $23 
million to decontaminate one Senate office building and $3 billion to 
decontaminate postal facilities and procure mail-sanitizing equipment. 
Deliberate introduction greatly increases the probability of a select 
agent becoming established and causing wide-ranging and devastating 
impacts to the economy, other disruptions to society, and diminished 
confidence in public and private institutions.
    The amended regulations will enhance the protection of human, 
animal, and plant health and safety. The final rules will reduce 
likelihood of the accidental or intentional release of a select agent 
or toxin. Benefits of the rules will derive from the greater 
probability that a release will be prevented from occurring.

Summary of the Estimated Maximum Additional Costs Attributable to the Final Rules for the Federal Government and
                                              Affected Entities \1\
----------------------------------------------------------------------------------------------------------------
                                              Unit cost             Number of units       Total additional cost
----------------------------------------------------------------------------------------------------------------
                                  Added Annual Cost for the Federal Government
----------------------------------------------------------------------------------------------------------------
Increased frequency of FBI/CJIS        $240 per person........  13,488 approved SRAs;    $432,000 per year \2\.
 background checks.                                              checks valid for three
                                                                 years.
----------------------------------------------------------------------------------------------------------------
                                 Added Recurring Costs for Affected Entities \3\
----------------------------------------------------------------------------------------------------------------
Submission of Security Plan..........   $4.95 per submission..  Estimated 130 annual     $643.50 per year.
                                                                 renewals.
Information Security \4\
    network connectivity monitoring    $24-$37 per license....  365 registered entities  $8,760-$13,505 per
     (encryption software).                                                               licensing period.
    network connectivity monitoring    $79-$199 per license...  365 registered entities  $28,835-$72,635 per
     (firewall software).                                                                 licensing period.
    malware software \4\ (intrusion    $15 per computer.......  365 registered entities  $5,475 per software
     detection).                                                                          update.
    malware software (antivirus).....  $80 per user per year..  13,488 approved SRAs...  $1,079,040 per year.
    system software updates            $2,400 per year........  365 registered entities  $876,000 per year.
     (dedicated time for IT
     Specialist).
----------------------------------------------------------------------------------------------------------------
        Total \5\....................      approximately $2 million annually, or on average about $5,500 per
                                                                   registered entity.
----------------------------------------------------------------------------------------------------------------
                      Added Costs for Entities that have a Tier 1 Select Agent or Toxin 3,6
----------------------------------------------------------------------------------------------------------------
Pre-suitability Assessment...........  $100-$120 per person...  13,488 approved SRAs...  $1.35-1.62 million.
Occupational Health Program..........  $107-$204 per person...  13,488 approved SRAs...  $1.44-2.75 million.
----------------------------------------------------------------------------------------------------------------

[[Page 61108]]

 
        Total \7\....................     approximately $2.8 million-$4.4 million, or on average about $9,600-
                                                    $15,100 per entity with a Tier 1 agent or toxin
----------------------------------------------------------------------------------------------------------------
\1\ The costs for registered entities summarized in this table are the estimated maximum additional expenditures
  that would be incurred, if none of the entities currently meets any of the additional security requirements
  set forth in the final rules. In addition, there will be the opportunity cost of additional time required to
  modify biosecurity and incident response plans and to conduct audits. Entities will be required to conduct
  complete inventory audits of all select agents and toxins in long-term storage upon the physical relocation of
  a collection or inventory of select agents or toxins, upon the departure or arrival of a principal
  investigator for those select agents or toxins, or in the event of a theft or loss of a select agent or toxin.
  Time costs are noted qualitatively in the Benefits and Costs section of this analysis.
\2\ The annual additional cost estimate assumes a uniform distribution of the 13,488 background checks over
  three years.
\3\ Based on site inspections, many of the entities currently have provisions in place similar or equivalent to
  those required.
\4\ Several of the recurring costs are associated with technological updating of information security, such as
  firewall and malware software updates. Estimated costs across all entities are uncertain as information is
  unavailable regarding the number of computers per affected entity. The estimates assume a single computer per
  entity is used for covered work.
\5\ Assumes costs of licensing and software updates are incurred annually.
\6\ Estimated costs are likely overstated as not all SRA-approved individuals will have access to Tier 1 select
  agents and toxins.
\7\ Average cost per entity is based on 292 entities that are registered to possess a Tier 1 agent or toxin.

B. Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) 
requires an agency to consider the potential impact of its regulations 
on small entities, including small businesses, small governmental 
units, and small not-for-profit organizations. We have prepared an 
economic analysis for this rule. The economic analysis provides a cost-
benefit analysis, as required by Executive Order 12866, and a final 
regulatory flexibility analysis that examines the potential economic 
effects of this rule on small entities, as required by the Regulatory 
Flexibility Act. Based on the economic analysis, which is available at 
www.selectagents.gov, we do not expect the rule to have a significant 
economic impact on small entities. In the absence of significant 
economic impacts, we have not identified alternatives that would 
minimize such impacts.

C. Paperwork Reduction Act of 1995

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), the information collection or 
recordkeeping requirements included in this final rule will be reviewed 
by the Office of Management and Budget (OMB) as a revision to existing 
OMB Control Number 0920-0576, expiration 10/31/2014.
    USDA/APHIS and HHS/CDC are asking OMB to approve, for 3 years, the 
use of these information collections, associated with its efforts to 
more closely regulate select agents or toxins that could be used to 
commit acts of domestic or international terrorism. We are soliciting 
comments from the public (as well as affected agencies) concerning this 
information collection activity. USDA/APHIS and HHS/CDC need this 
outside input to help accomplish the following:
    (1) Evaluate whether the proposed information collection is 
necessary for the proper performance of our agency's functions, 
including whether the information will have practical utility;
    (2) Evaluate the accuracy of our estimate of the burden of the 
proposed information collection, including the validity of the 
methodology and assumptions used;
    (3) Enhance the quality, utility, and clarity of the information to 
be collected; and
    (4) Minimize the burden of the information collection on those who 
are to respond (such as through the use of appropriate automated, 
electronic, mechanical, or other technological collection techniques or 
other forms of information technology; e.g., permitting electronic 
submission of responses).
    Estimate of burden: Public reporting burden for this collection of 
information is estimated to average 2.3187883 hours per response.
    Respondents: Researchers, universities, research and development 
organizations, commercial manufacturers, non-profit institutions, 
diagnostic laboratories and other interested parties who possess, use, 
or transfer agents or toxins deemed a severe threat to human, animal or 
plant health, or to animal or plant products.
    Estimated annual number of respondents: 386.
    Estimated annual number of responses per respondent: 12.
    Estimated annual number of responses: 4,721.
    Estimated total annual burden on respondents: 10,947 hours. (Due to 
averaging, the total annual burden hours may not equal the product of 
the annual number of responses multiplied by the reporting burden per 
response.)

----------------------------------------------------------------------------------------------------------------
                                                                                      Average
                                                     Number of       Number of      burden per     Total burden
            Section                 Form name       respondents    responses per   response  (in       hours
                                                                    respondent        hours)
----------------------------------------------------------------------------------------------------------------
9 CFR 121.5 and 6, 7 CFR        Report of                    161               3               1             299
 331.5, 43 CFR 73.5 and 6.       Identification
                                 of a Select
                                 Agent or Toxin.
Sec.   121.7, Sec.   331.7,     Application for                7               1               5              35
 Sec.   73.7.                    Registration.
Sec.   121.7, Sec.   331.7,     Amendment to a               380               7               1           2,660
 Sec.   73.7.                    Certificate of
                                 Registration.
Sec.   121.11, Sec.   331.11,   Security Plan...             380               1               5           1,900
 Sec.   73.11.
Sec.   121.12, Sec.   331.12,   Biosafety/                   380               1               8           3,040
 Sec.   73.12.                   Biocontainment
                                 Plan.
Sec.   121.13, Sec.   331.13,   Request                      160               1               2             320
 Sec.   73.13.                   Regarding a
                                 Restricted
                                 Experiment.
Sec.   121.14, Sec.   331.14,   Incident                     380               1               5           1,900
 Sec.   73.14.                   Response Plan.
Sec.   121.15, Sec.   331.15,   Training........             380               1               1             380
 Sec.   73.15.

[[Page 61109]]

 
Sec.   121.16, Sec.   331.16,   Request to                   290               1               2             580
 Sec.   73.16.                   Transfer Select
                                 Agents and
                                 Toxins.
Sec.   121.17, Sec.   331.17,   Records.........             295               1             0.5             148
 Sec.   73.17.
Sec.   121.19, Sec.   331.19,   Notification of              195               1               2             390
 Sec.   73.19.                   Theft, Loss, or
                                 Release.
----------------------------------------------------------------------------------------------------------------

    Copies of this information collection may be obtained by calling 
the CDC Reports Clearance Officer at (404) 639-5960 or sending an email 
to omb@cdc.gov. HHS/CDC is requesting continued OMB approval to collect 
this information through the use of five updated forms. These forms 
are: (1) Application for Registration, (2) Transfer of Select Agent or 
Toxin Form, (3) Facility Notification of Theft, Loss, or Release Form, 
(4) Clinical and Diagnostic Laboratory Reporting Form, and (5) Request 
for Exemption.

D. Executive Order 12988: Civil Justice Reform

    This rule has been reviewed under Executive Order 12988, Civil 
Justice Reform. Once the final rule is in effect: (1) All State and 
local laws and regulations that are inconsistent with this rule will be 
preempted; (2) no retroactive effect will be given to this rule; and 
(3) administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

E. Executive Order 13132: Federalism

    This rule has been reviewed under Executive Order 13132, 
Federalism. The review reveals that this regulation will not have 
substantial and direct effects on Tribal governments and will not have 
significant Tribal implications.

F. Plain Writing Act of 2010

    Under Public Law 111-274 (October 13, 2010), HHS has attempted to 
use plain language in promulgating the rule consistent with the Plain 
Writing Act guidelines.

IV. References

1. Delgado, Erickson, et al., 2008. Chapare virus, a newly discovered 
arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. 
PLoS Pathogens 4:e1000047.
2. Briese T, Paweska JT, McMullan LK, Hutchison SK, Street C, Palacios 
G, Khristova ML, Weyer J, Swanepoel R, Egholm M, Nichol ST, Lipkin WI. 
Genetic detection and characterization of Lujo virus, a new hemorrhagic 
fever-associated arenavirus from southern Africa. PLoS 2009 May; 
5(5):e1000455. Epub 2009 May 29. Available at www.plospathogens.org.
3. World Health Organization. Summary of probable SARS cases with onset 
of illness from 1 November 2002 to 31 July 2003 [monograph on the 
Internet]. 2003 Dec 31 [cited 2004 Aug 26]. Available from http://www.who.int/csr/sars/country/table2004_04_21/en/
4. World Health Organization. SARS case in laboratory worker in Taiwan, 
China [monograph on the Internet]. 2003 Dec 17 [cited 2004 Aug 26]. 
Available from http://www.who.int/mediacentre/releases/2003/np26/en/
5. World Health Organization. China confirms SARS infection in another 
previously reported case: summary of cases to date--Update 5 [monograph 
on the Internet]. 2004 Apr 30 [cited 2004 Aug 26]. Available from 
http://www.who.int/csr/don/2004_04_30/en/
6. World Health Organization. China's latest SARS outbreak has been 
contained, but biosafety concerns remain--Update 7 [monograph on the 
Internet]. 2004 May 18. Available from http://www.who.int/csr/don/2004_05_18a/en/index.html
7. Liang, G., Chen, Q., Xu, J., Liu, Y., Lim, W., Peiris, J. S., 
Anderson, L. J., Ruan, L., Li, H., Kan, B., et al. Laboratory diagnosis 
of four recent sporadic cases of community-acquired SARS, Guangdong 
Province, China. (2004) Emerg. Infect. Dis. 10, 1774-1781.
8. Sayeed et al. Epsilon-toxin is required for most Clostridium 
perfringens type D vegetative culture supernatants to cause lethality 
in the mouse intravenous injection model. Infect Immun. 2005 
Nov;73(ll):7413-21
9. Favreau P, Krimm I, Le Gall F, Bobenrieth MJ, Lamthanh H, Bouet F, 
Servent D, Molgo J, M[eacute]nez A, Letourneux Y, Lancelin JM. 
Biochemical Characterization and Nuclear Magnetic Resonance Structure 
of Novel [alpha]-Conotoxins Isolated from the Venom of Conus consors. 
Biochemistry. 1999 May 11;38(19):6317-26
10. Groebe DR, Dumm JM, Levitan ES, Abramson SN. alpha-Conotoxins 
selectively inhibit one of the two acetylcholine binding sites of 
nicotinic receptors. Mol Pharmacol. 1995 Jul;48(1):105-11.
11. Groebe DR, Gray WR, Abramson SN. Determinants Involved in the 
Affinity of [alpha] -Conotoxins GI and SI for the Muscle Subtype of 
Nicotinic Acetylcholine Receptors. Biochemistry. 1997 May 
27;36(21):6469-74.
12. Liu L, Chew G, Hawrot E, Chi C, Wang C. Two potent alpha3/5 
conotoxins from piscivorous Conus achatinus. Acta Biochim Biophys Sin 
(Shanghai). 2007 Jun; 39(6):438-44.
13. Acetylcholine Receptor Binding-Characteristics of Snake and Cone 
Snail Venom Postsynaptic Neurotoxins: Further Studies with a Non-
radiological Assay. Bradley G. Stiles. Toxicon. 1993 Jul;31(7):825-34.
14. Galgiani, J.N. 1999. Coccidiomycosis: a regional disease of 
national importance. Ann Intern. Med. 130:293-298.
15. Chen N., et al. 2005. Virulence differences between monkeypox virus 
isolates from West Africa and the Congo basin. Virology 340:46-63.
16. Hutson C. L., et al. 2009. A prairie dog animal model of systemic 
orthopoxvirus disease using West African and Congo Basin strains of 
monkeypox virus. J. Gen. Virol. 90:323-333.
17. Saijo M., et al. 2009. Virulence and pathophysiology of the Congo 
Basin and West African strains of monkeypox virus in non-human 
primates. J. Gen. Virol. 90:2266-2271.
18. Sbrana E., Xiao S. Y., Newman P. C., Tesh R. B. 2007. Comparative 
pathology of North American and central African strains of monkeypox 
virus in a ground squirrel model of the disease. Am. J. Trop. Med. Hyg. 
76:155-164.
19. Likos AM, Sammons SA, Olson VA, Frace AM, Li Y, Olsen-Rasmussen M, 
Davidson W, Galloway R,

[[Page 61110]]

Khristova ML, Reynolds MG, Zhao H, Carroll DS, Curns A, Formenty P, 
Esposito JJ, Regnery RL, Damon IK. A tale of two clades: monkeypox 
viruses. J Gen Virol. 2005 Oct; 86(Pt 10):2661-72.
20. Azad and Radulovic, 2003: Azad AF, Radulovic S Pathogenic 
rickettsiae as bioterrorism agents. Ann N Y Acad Sci. 2003; 990: 734--
738.
21. Gres[iacute]kov[aacute] M, Kaluzov[aacute] M, 1997. Biology of 
tick-borne encephalitis virus. Acta Virol. Apr;41(2):115-24.
22. Ecker M, Allison SL, Meixner T, Heinz FX, 1999. Sequence analysis 
and genetic classification of tick-borne encephalitis viruses from 
Europe and Asia. J Gen Virol. Jan;80 (Pt 1):179-85.
23. Raoult D, Houpikian P, Tissot DH, Riss JM, Arditi-Djiane J, Brouqui 
P. Treatment of Q fever endocarditis: comparison of 2 regimens 
containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern 
Med. 1999;159(2):167-73
24. National Science Advisory Board for Biosecurity report: ``Enhancing 
Personnel Reliability among Individuals with Access to Select Agents'' 
(http://oba.od.nih.gov/biosecurity/meetings/200905T/NSABB%20Final%20Report%20on%20PR%205-29-09.pdf).
25. Responsible Research with Biological Select Agents and Toxins, 
Committee on Laboratory Security and Personnel Reliability Assurance 
Systems for Laboratories Conducting Research on Biological Select 
Agents and Toxins, National Research Council of the National Academies 
(http://www8.nationalacademies.org/cp/projectview.aspx?key=49097).
26. Report of the Working Group on Strengthening the Biosecurity of the 
United States, Executive Order 13486 Working Group (http://edocket.access.gpo.gov/2009/pdf/E9-818.pdf).
27. Defense Science Board Task Force on Department of Defense 
Biological Safety and Security Program (http://www.acq.osd.mil/dsb/reports/ADA499977.pdf).
28. Biosafety in Microbiological and Biomedical Laboratories (http://www.cdc.gov/biosafety/publications/bmbl5/index.htm).

List of Subjects in 42 CFR Part 73

    Biologics, Packaging and containers, Penalties, Reporting and 
recordkeeping requirements, Transportation.

    Dated: September 28, 2012.
Kathleen Sebelius,
Secretary.
    For the reasons stated in the preamble, the Centers for Disease 
Control and Prevention, United States Department of Health and Human 
Services, amends 42 CFR part 73 as follows:

PART 73--POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS

0
1. The authority citation for part 73 continues to read as follows:

    Authority:  42 U.S.C. 262a; sections 201-204, 221 and 231 of 
Title II of Public Law 107-188, 116 Stat. 637 (42 U.S.C. 262a).


0
2. Add Sec.  73.0 to read as set forth below.


Sec.  73.0  Applicability and related requirements.

    All individuals and entities that possess SARS-CoV, Lujo virus, or 
Chapare virus must provide notice to CDC regarding their possession of 
SARS-CoV, Lujo virus, or Chapare virus on or before November 5, 2012. 
Currently registered individuals and entities possessing SARS-CoV, Lujo 
virus, or Chapare virus must meet all the requirements of this part by 
December 4, 2012. All previously unregistered individuals and entities 
possessing SARS-CoV, Lujo virus, or Chapare virus must meet all of the 
requirements of this part by April 3, 2013.

0
3. Section 73.1 is amended by adding, in alphabetical order, 
definitions of Conotoxins, Information security, Occupational exposure, 
Recombinant nucleic acids, Security barrier, and Synthetic nucleic 
acids to read as set forth below.


Sec.  73.1  Definitions.

* * * * *
    Conotoxins means short, paralytic alpha conotoxins containing the 
following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7, whereas:

(1) C = Cysteine residues are all present as disulfides, with the 
1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming specific 
disulfide bridges;
(2) The consensus sequence includes known toxins [alpha]-MI and 
[alpha]-GI (shown above) as well as [alpha]-GIA, Ac1.1a, [alpha]-
CnIA, [alpha]-CnIB;
(3) X1 = any amino acid(s) or Des-X;
(4) X2 = Asparagine or Histidine;
(5) P = Proline;
(6) A = Alanine;
(7) G = Glycine;
(8) X3 = Arginine or Lysine;
(9) X4 = Asparagine, Histidine, Lysine, Arginine, 
Tyrosine, Phenylalanine or Tryptophan;
(10) X5 = Tyrosine, Phenylalanine, or Tryptophan;
(11) X6 = Serine, Threonine, Glutamate, Aspartate, 
Glutamine, or Asparagine;
(12) X7 = Any amino acid(s) or Des X; and
(13) ``Des X'' = ``an amino acid does not have to be present at this 
position.'' For example if a peptide sequence were XCCHPA then the 
related peptide CCHPA would be designated as Des-X.
* * * * *
    Information security means protecting information and information 
systems from unauthorized access, use, disclosure, disruption, 
modification, or destruction in order to provide--
    (1) Integrity, which means guarding against improper information 
modification or destruction, and includes ensuring information 
authenticity;
    (2) Confidentiality, which means preserving authorized restrictions 
on access and disclosure, including means for protecting personal 
privacy and proprietary information; and
    (3) Availability, which means ensuring timely and reliable access 
to and use of information.
    Occupational exposure means any reasonably anticipated skin, eye, 
mucous membrane, parenteral contact, or respiratory aerosol exposure to 
select agents or toxins that may result from the performance of an 
employee's duties.
* * * * *
    Recombinant nucleic acids means:
    (1) Molecules that are constructed by joining nucleic acid 
molecules and that can replicate in a living cell or
    (2) Molecules that result from the replication of those described 
in paragraph (1) of this definition.
* * * * *
    Security barrier means a physical structure that is designed to 
prevent entry by unauthorized persons.
* * * * *
    Synthetic nucleic acids means:
    (1) Molecules that are chemically or by other means synthesized or 
amplified, including those that are chemically or otherwise modified 
but can base pair with naturally occurring nucleic acid molecules 
(i.e., synthetic nucleic acids) or
    (2) Molecules that result from the replication of those described 
in paragraph (1) of this definition.
* * * * *

0
4. Section 73.3 is amended as follows:
0
a. By adding a sentence to the end of paragraph (a) to read as set 
forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. In paragraph (c) introductory text, by adding the phrase ``and/or 
Synthetic'' after the word ``Recombinant'' each time it appears.

[[Page 61111]]

0
d. In paragraph (c)(2) introductory text, by adding the phrase ``and/or 
synthetic'' after the word ``Recombinant.''
0
e. By revising paragraph (d)(3) to read as set forth below.
0
f. By adding a new paragraph (d)(4) to read as set forth below.
0
g. By adding a new paragraph (d)(5) to read as set forth below.
0
h. By revising paragraph (e) to read as set forth below.
0
i. In paragraph (f)(3)(i), by removing the words ``Lassa fever virus'' 
and ``South American Haemorrhagic Fever virus (Junin, Machupo, Sabia, 
Flexal, Guanarito)'' and by adding, after ``Botulinum neurotoxins,'', 
the term ``Botulinum neurotoxin producing species of Clostridium.''


Sec.  73.3  HHS select agents and toxins.

    (a) * * * The select agents and toxins marked with an asterisk (*) 
are designated as Tier 1 select agents and toxins and are subject to 
additional requirements as listed in this part.
    (b) HHS select agents and toxins:

Abrin
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Conotoxins (Short, paralytic alpha conotoxins containing the following 
amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7)
Coxiella burnetii
Crimean-Congo haemorrhagic fever virus
Diacetoxyscirpenol
Eastern Equine Encephalitis virus
Ebola virus*
Francisella tularensis*
Lassa fever virus
Lujo virus
Marburg virus*
Monkeypox virus
Reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments (Reconstructed 1918 Influenza virus)
Ricin
Rickettsia prowazekii
SARS-associated coronavirus (SARS-CoV)
Saxitoxin
South American Haemorrhagic Fever viruses:
    Chapare
    Guanarito Junin
    Machupo
    Sabia
Staphylococcal enterotoxins (subtypes A-E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
    Far Eastern subtype
    Siberian subtype
Kyasanur Forest disease virus
Omsk haemorrhagic fever virus
Variola major virus (Smallpox virus) *
Variola minor virus (Alastrim) *
Yersinia pestis *
* * * * *
    (d) * * *
    (3) Except as required in Sec.  73.16(l), the aggregate amount of 
the toxin under the control of a principal investigator, treating 
physician or veterinarian, or commercial manufacturer or distributor 
does not, at any time, exceed the following amounts: 100 mg of Abrin; 
0.5 mg of Botulinum neurotoxins; 100 mg of Conotoxins (Short, paralytic 
alpha conotoxins containing the following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7); 1,000 mg of Diacetoxyscirpenol; 100 mg of 
Ricin; 100 mg of Saxitoxin; 5 mg of Staphylococcal enterotoxins 
(subtypes A-E); 1,000 mg of T-2 toxin; or 100 mg of Tetrodotoxin.
    (i) The amounts are transferred only after the transferor uses due 
diligence and documents that the recipient has a legitimate need (i.e., 
reasonably justified by a prophylactic, protective, bona fide research, 
or other peaceful purpose) to handle or use such toxins. 
Notwithstanding the provisions of paragraph (d) of this section, the 
HHS Secretary retains the authority to, without prior notification, 
inspect and copy or request the submission of the due diligence 
documentation to the CDC.
    (ii) Reports to CDC if they detect a known or suspected violation 
of Federal law or become aware of suspicious activity related to a 
toxin listed in this part.
    (4) An animal inoculated with or exposed to an HHS select toxin.
    (5) Any South American genotypes of Eastern Equine Encephalitis 
Virus and any West African Clade of Monkeypox virus provided that the 
individual or entity can verify that the agent is within the exclusion 
category.
    (e) An attenuated strain of a select agent or an inactive form of a 
select toxin may be excluded from the requirements of this part based 
upon a determination by the HHS Secretary that the attenuated strain or 
inactivated toxin does not pose a severe threat to public health and 
safety.
    (1) To apply for exclusion, an individual or entity must submit a 
written request and supporting scientific information. A written 
decision granting or denying the request will be issued. An exclusion 
will be effective upon notification to the applicant. Exclusions will 
be listed on the National Select Agent Registry Web site at http://www.selectagents.gov/.
    (2) If an excluded attenuated strain or inactivated toxin is 
subjected to any manipulation that restores or enhances its virulence 
or toxic activity, the resulting select agent or toxin will be subject 
to the requirements of this part.
* * * * *

0
5. Section 73.4 is amended as follows:
0
a. By adding a sentence to the end of paragraph (a) to read as set 
forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. In paragraph (c) introductory text, by adding the phrase ``and/or 
Synthetic'' after the word ``Recombinant'' each time it appears.
0
d. In paragraph (c)(2) introductory text, by adding the phrase ``and/or 
synthetic'' after the word ``Recombinant.''
0
e. By adding a new paragraph (d)(3) to read as set forth below.
0
f. By revising paragraph (e) to read as set forth below.
0
g. In paragraph (f)(3)(i), by removing the words ``Brucella melitensis, 
Hendra virus, Nipah virus, Rift Valley fever virus, and Venezuelan 
equine encephalitis virus'' and adding, after ``Bacillus anthracis'', 
the terms ``Burkholderia mallei'' and ``Burkholderia pseudomallei'' in 
their place.


Sec.  73.4  Overlap select agents and toxins.

    (a) * * * The select agents and toxins marked with an asterisk (*) 
are designated as Tier 1 select agents and toxins and are subject to 
additional requirements as listed in this part.
    (b) Overlap select agents and toxins:

Bacillus anthracis*;
Bacillus anthracis (Pasteur strain);
Brucella abortus;
Brucella melitensis;
Brucella suis;
Burkholderia mallei*;
Burkholderia pseudomallei*;
Hendra virus;
Nipah virus;
Rift Valley fever virus;
Venezuelan equine encephalitis virus
* * * * *
    (d) * * *
    (3) Any subtypes of Venezuelan equine encephalitis virus except for 
Subtypes IAB or IC provided that the individual or entity can verify 
that the agent is within the exclusion category.
    (e) An attenuated strain of a select agent or an inactive form of a 
select toxin may be excluded from the requirements of this part based 
upon a determination by the HHS Secretary or Administrator that the 
attenuated strain

[[Page 61112]]

or inactivated toxin does not pose a severe threat to public health and 
safety, to animal health or to animal products.
    (1) To apply for exclusion, an individual or entity must submit a 
written request and supporting scientific information. A written 
decision granting or denying the request will be issued. An exclusion 
will be effective upon notification to the applicant. Exclusions will 
be listed on the National Select Agent Registry Web site at http://www.selectagents.gov/.
    (2) If an excluded attenuated strain or inactivated toxin is 
subjected to any manipulation that restores or enhances its virulence 
or toxic activity, the resulting select agent or toxin will be subject 
to the requirements of this part.
* * * * *

0
6. Section 73.5 is amended as follows:
0
a. By amending paragraph (a)(3)(i) to remove the words ``Lassa fever 
virus'' and ``South American Haemorrhagic Fever viruses (Junin, 
Machupo, Sabia, Flexal, Guanarito)'' and by adding, after ``Botulinum 
neurotoxins,'' the term ``Botulinum neurotoxin producing species of 
Clostridium.''
0
b. By revising paragraph (e) to read as set forth below.


Sec.  73.5  Exemptions for HHS select agents and toxins.

* * * * *
    (e) The HHS Secretary may temporarily exempt an individual or 
entity from the requirements of this part based on a determination that 
the exemption is necessary to provide for the timely participation of 
the individual or entity in response to a domestic or foreign public 
health emergency. With respect to the emergency involved, the exemption 
may not exceed 30 calendar days, except that one extension of an 
additional 30 calendar days may be granted.

0
7. Section 73.6 is amended as follows:
0
a. By amending (a)(3)(i) to remove the words ``Brucella melitensis, 
Hendra virus, Nipah virus, Rift Valley fever virus, or Venezuelan 
equine encephalitis virus'' and adding, after ``Bacillus anthracis'', 
the terms ``Burkholderia mallei'' and ``Burkholderia pseudomallei'' in 
their place.
0
b. By revising paragraph (e) to read as set forth below.


Sec.  73.6  Exemptions for overlap select agents and toxins.

* * * * *
    (e) The HHS Secretary may temporarily exempt an individual or 
entity from the requirements of this part based on a determination that 
the exemption is necessary to provide for the timely participation of 
the individual or entity in response to a domestic or foreign public 
health emergency. With respect to the emergency involved, the exemption 
may not exceed 30 calendar days, except that one extension of an 
additional 30 calendar days may be granted.
* * * * *

0
8. Section 73.9 is amended as follows:
0
a. In paragraph (a)(4), by removing the word ``and.''
0
b. By redesignating paragraph (a)(5) as paragraph (a)(6).
0
c. By adding a new paragraph (a)(5) to read as set forth below.
0
d. By revising the first sentence of paragraph (b) to read as set forth 
below.
0
e. In paragraph (c)(1), by removing the words ``Brucella melitensis,'' 
``Hendra virus,'' ``Lassa fever virus,'' ``Nipah virus,'' ``Rift Valley 
fever virus,'' ``South American Haemorrhagic Fever viruses (Junin, 
Machupo, Sabia, Flexal, Guanarito),'' and ``Venezuelan equine 
encephalitis virus'' and adding, after ``Botulinum neurotoxins,'' the 
terms ``Botulinum neurotoxin producing species of Clostridium, 
Burkholderia mallei, Burkholderia pseudomallei''.


Sec.  73.9  Responsible Official.

    (a) * * *
    (5) Have a physical (and not merely a telephonic or audio/visual) 
presence at the registered entity to ensure that the entity is in 
compliance with the select agent regulations and be able to respond in 
a timely manner to onsite incidents involving select agents and toxins 
in accordance with the entity's incident response plan, and
* * * * *
    (b) An entity may designate one or more individuals to serve as an 
alternate Responsible Official, who acts for the Responsible Official 
in his/her absence. * * *
* * * * *

0
9. Section 73.10 is amended as follows:
0
a. By redesignating paragraphs (e) through (j) as paragraphs (f) 
through (k) respectively.
0
b. By adding a new paragraph (e) to read as set forth below.
0
c. In newly redesignated paragraph (j), by removing the word ``five'' 
and adding in its place ``three''.


Sec.  73.10  Restricting access to select agents and toxins; security 
risk assessments.

* * * * *
    (e) A person with a valid approval from the HHS Secretary or 
Administrator to have access to select agents and toxins may request, 
through his or her Responsible Official, that the HHS Secretary or 
Administrator provide their approved access status to another 
registered individual or entity for a specified period of time.
* * * * *

0
10. Section 73.11 is amended as follows:
0
a. By revising paragraph (b) to read as set forth below.
0
b. By revising paragraph (c)(2) to read as set forth below.
0
c. By adding new paragraphs (c)(8), (c)(9), and (c)(10) to read as set 
forth below.
0
d. By redesignating paragraphs (e) and (f) as paragraphs (g) and (h), 
respectively and by revising newly redesignated paragraph (g) to read 
as set forth below.
0
e. By adding new paragraphs (e) and (f) to read as set forth below.


Sec.  73.11  Security.

* * * * *
    (b) The security plan must be designed according to a site-specific 
risk assessment and must provide graded protection in accordance with 
the risk of the select agent or toxin, given its intended use. A 
current security plan must be submitted for initial registration, 
renewal of registration, or when requested.
    (c) * * *
    (2) Contain provisions for the control of access to select agents 
and toxins, including the safeguarding of animals, including 
arthropods, or plants intentionally or accidentally exposed to or 
infected with a select agent, against unauthorized access, theft, loss 
or release.
* * * * *
    (8) Describe procedures for how the Responsible Official will be 
informed of suspicious activity that may be criminal in nature and 
related to the entity, its personnel, or its select agents or toxins; 
and describe procedures for how the entity will notify the appropriate 
Federal, State, or local law enforcement agencies of such activity.
    (9) Contain provisions for information security that:
    (i) Ensure that all external connections to systems which manage 
security for the registered space are isolated or have controls that 
permit only authorized and authenticated users;
    (ii) Ensure that authorized and authenticated users are only 
granted access to select agent and toxin related information, files, 
equipment (e.g., servers or mass storage devices) and applications as 
necessary to fulfill their roles and responsibilities, and that access 
is modified when the user's roles and responsibilities change or when

[[Page 61113]]

their access to select agents and toxins is suspended or revoked;
    (iii) Ensure that controls are in place that are designed to 
prevent malicious code (such as, but not limited to, computer virus, 
worms, spyware) from compromising the confidentiality, integrity, or 
availability of information systems which manage access to registered 
spaces in Sec.  73.11 or records in Sec.  73.17;
    (iv) Establish a robust configuration management practice for 
information systems to include regular patching and updates made to 
operating systems and individual applications; and
    (v) Establish procedures that provide backup security measures in 
the event that access control systems, surveillance devices, and/or 
systems that manage the requirements of section 17 of this part are 
rendered inoperable.
    (10) Contain provisions and policies for shipping, receiving, and 
storage of select agents and toxins, including documented procedures 
for receiving, monitoring, and shipping of all select agents and 
toxins. These provisions must provide that an entity will properly 
secure containers on site and have a written contingency plan for 
unexpected shipments.
* * * * *
    (e) Entities must conduct complete inventory audits of all affected 
select agents and toxins in long-term storage when any of the following 
occur:
    (1) Upon the physical relocation of a collection or inventory of 
select agents or toxins for those select agents or toxins in the 
collection or inventory;
    (2) Upon the departure or arrival of a principal investigator for 
those select agents and toxins under the control of that principal 
investigator; or
    (3) In the event of a theft or loss of a select agent or toxin, all 
select agents and toxins under the control of that principal 
investigator.
    (f) In addition to the requirements contained in paragraphs (c) and 
(d) of this section, the security plan for an individual or entity 
possessing a Tier 1 select agent or toxin must also:
    (1) Describe procedures for conducting a pre-access suitability 
assessment of persons who will have access to a Tier 1 select agent or 
toxin;
    (2) Describe procedures for how an entity's Responsible Official 
will coordinate their efforts with the entity's safety and security 
professionals to ensure security of Tier 1 select agents and toxins and 
share, as appropriate, relevant information; and
    (3) Describe procedures for the ongoing assessment of the 
suitability of personnel with access to a Tier 1 select agent or toxin. 
The procedures must include:
    (i) Self- and peer-reporting of incidents or conditions that could 
affect an individual's ability to safely have access to or work with 
select agents and toxins, or to safeguard select agents and toxins from 
theft, loss, or release;
    (ii) The training of employees with access to Tier 1 select agents 
and toxins on entity policies and procedures for reporting, evaluation, 
and corrective actions concerning the assessment of personnel 
suitability; and
    (iii) The ongoing suitability monitoring of individuals with access 
to Tier 1 select agents and toxins.
    (4) Entities with Tier 1 select agents and toxins must prescribe 
the following security enhancements:
    (i) Procedures that will limit access to a Tier 1 select agent or 
toxin to only those individuals who are approved by the HHS Secretary 
or Administrator, following a security risk assessment by the Attorney 
General, have had an entity-conducted pre-access suitability 
assessment, and are subject to the entity's procedures for ongoing 
suitability assessment;
    (ii) Procedures that limit access to laboratory and storage 
facilities outside of normal business hours to only those specifically 
approved by the Responsible Official or designee;
    (iii) Procedures for allowing visitors, their property, and 
vehicles at the entry and exit points to the registered space, or at 
other designated points of entry to the building, facility, or compound 
that are based on the entity's site-specific risk assessment;
    (iv) A minimum of three security barriers where each security 
barrier adds to the delay in reaching secured areas where select agents 
and toxins are used or stored. One of the security barriers must be 
monitored in such a way as to detect intentional and unintentional 
circumventing of established access control measures under all 
conditions (day/night, severe weather, etc.) The final barrier must 
limit access to the select agent or toxin to personnel approved by the 
HHS Secretary or Administrator, following a security risk assessment by 
the Attorney General.
    (v) All registered space or areas that reasonably afford access to 
the registered space must be protected by an intrusion detection system 
(IDS) unless physically occupied;
    (vi) Personnel monitoring the IDS must be capable of evaluating and 
interpreting the alarm and alerting the designated security response 
force or law enforcement;
    (vii) For powered access control systems, describe procedures to 
ensure that security is maintained in the event of the failure of 
access control systems due to power disruption affecting registered 
space;
    (viii) The entity must:
    (A) Determine that the response time for security forces or local 
police will not exceed 15 minutes or
    (B) Provide security barriers that are sufficient to delay 
unauthorized access until the response force arrives in order to 
safeguard the select agents and toxins from theft, intentional release, 
or unauthorized access. The response time is measured from the time of 
an intrusion alarm, or report of a security incident, to the arrival of 
the responders at the first security barrier.
    (5) Entities that possess Variola major virus and Variola minor 
virus must have the following additional security requirements:
    (i) Require personnel with independent unescorted access to Variola 
major or Variola minor virus to have a Top Secret security clearance;
    (ii) Require Variola major or Variola minor virus storage locations 
to be under the surveillance of closed circuit television that is 
monitored;
    (iii) After hours access procedures for Variola major or Variola 
minor virus must require notification of the entity's security staff 
prior to entry into the Variola laboratory and upon exit;
    (iv) Require that observation zones be maintained in outdoor areas 
adjacent to the physical barrier at the perimeter of the entity and be 
large enough to permit observation of the activities of people at that 
barrier in the event of its penetration;
    (v) Provide for a minimum of four barriers for the protection of 
the Variola major or Variola minor virus, one of which must be a 
perimeter fence;
    (vi) Require a numbered picture badge identification subsystem to 
be used for all individuals who are authorized to access Variola major 
or Variola minor without escort;
    (vii) Require the use, at all times, of properly trained and 
equipped security force personnel able to interdict threats identified 
in the site specific risk assessment;
    (viii) Identify security force personnel designated to strengthen 
onsite response capabilities, and that will be onsite and available at 
all times to carry out their assigned response duties;
    (ix) Provide for security patrols to periodically check external 
areas of the registered areas to include physical barriers and building 
entrances;
    (x) Require that all on-duty security force personnel shall be 
capable of

[[Page 61114]]

maintaining continuous communication with support and response assets 
by way of security operations center;
    (xi) Require that Variola major and Variola minor material in long 
term storage be stored in tamper-evident systems;
    (xii) Require that all spaces containing working or permanent 
Variola major or Variola minor stocks be locked and protected by an 
intrusion alarm system that will alarm upon the unauthorized entry of a 
person anywhere into the area;
    (xiii) Require that alarms required pursuant to this section 
annunciate in a continuously manned security operations center located 
within the facility; and
    (xiv) Require that the security operations center shall be located 
within a building so that the interior is not visible from the 
perimeter of the protected area.
    (g) In developing a security plan, an individual or entity should 
consider the document entitled, ``Security Guidance for Select Agent or 
Toxin Facilities.'' The document is available on the National Select 
Agent Registry Web site at http://www.selectagents.gov/.
* * * * *

0
11. Section 73.12 is amended as follows:
0
a. By revising paragraph (a) to read as set forth below.
0
b. By revising paragraphs (c)(1), (2), and (3) to read as set forth 
below.
0
c. By redesignating paragraph (d) as paragraph (e).
0
d. By adding a new paragraph (d) to read as set forth below.


Sec.  73.12  Biosafety.

    (a) An individual or entity required to register under this part 
must develop and implement a written biosafety plan that is 
commensurate with the risk of the select agent or toxin, given its 
intended use. The biosafety plan must contain sufficient information 
and documentation to describe the biosafety and containment procedures 
for the select agent or toxin, including any animals (including 
arthropods) or plants intentionally or accidentally exposed to or 
infected with a select agent.
* * * * *
    (c) * * *
    (1) The CDC/NIH publication, ``Biosafety in Microbiological and 
Biomedical Laboratories.'' This document is available on the National 
Select Agent Registry Web site at  http://www.selectagents.gov.
    (2) The Occupational Safety and Health Administration (OSHA) 
regulations in 29 CFR parts 1910.1200 and 1910.1450. This document is 
available on the National Select Agent Registry Web site at http://www.selectagents.gov.
    (3) The ``NIH Guidelines for Research Involving Recombinant DNA 
Molecules,'' (NIH Guidelines). This document is available on the 
National Select Agent Registry Web site at  http://www.selectagents.gov.
* * * * *
    (d) The biosafety plan must include an occupational health program 
for individuals with access to Tier 1 select agents and toxins, and 
those individuals must be enrolled in the occupational health program.
* * * * *

0
12. Section 73.13 is amended as follows:
0
a. In paragraph (a), add the phrase ``, or possess products (i.e., 
select agents that are not known to acquire the resistance naturally, 
if such acquisition could compromise the control of disease agents in 
humans, veterinary medicine, or agriculture, or recombinant and/or 
synthetic nucleic acids containing genes for the biosynthesis of select 
toxins lethal for vertebrates at an LD[50] < 100 ng/kg body weight) 
resulting from,'' after the word ``conduct'' both times it appears.
0
b. By revising paragraph (b) to read as set forth below.


Sec.  73.13  Restricted experiments.

* * * * *
    (b) Restricted experiments:
    (1) Experiments that involve the deliberate transfer of, or 
selection for, a drug resistance trait to select agents that are not 
known to acquire the trait naturally, if such acquisition could 
compromise the control of disease agents in humans, veterinary 
medicine, or agriculture.
    (2) Experiments involving the deliberate formation of synthetic or 
recombinant nucleic acids containing genes for the biosynthesis of 
select toxins lethal for vertebrates at an LD[50] < 100 ng/kg body 
weight.
* * * * *

0
13. Section 73.14 is amended as follows:
0
a. By revising paragraph (a) to read as set forth below.
0
b. By revising paragraph (b) to read as set forth below.
0
c. By redesignating paragraphs (c) and (d) as paragraphs (d) and (f) 
respectively.
0
d. By adding a new paragraph (c) to read as set forth below.
0
e. By adding a new paragraph (e) to read as set forth below.


Sec.  73.14  Incident response.

    (a) An individual or entity required to register under this part 
must develop and implement a written incident response plan based upon 
a site specific risk assessment.\2\ The incident response plan must be 
coordinated with any entity-wide plans, kept in the workplace, and 
available to employees for review.
---------------------------------------------------------------------------

    \2\ Nothing in this section is meant to supersede or preempt 
incident response requirements imposed by other statutes or 
regulations.
---------------------------------------------------------------------------

    (b) The incident response plan must fully describe the entity's 
response procedures for the theft, loss, or release of a select agent 
or toxin; inventory discrepancies; security breaches (including 
information systems); severe weather and other natural disasters; 
workplace violence; bomb threats and suspicious packages; and 
emergencies such as fire, gas leak, explosion, power outage, and other 
natural and man-made events.
    (c) The response procedures must account for hazards associated 
with the select agent or toxin and appropriate actions to contain such 
select agent or toxin, including any animals (including arthropods) or 
plants intentionally or accidentally exposed to or infected with a 
select agent.
* * * * *
    (e) Entities with Tier 1 select agents and toxins must have the 
following additional incident response policies or procedures:
    (1) The incident response plan must fully describe the entity's 
response procedures for failure of intrusion detection or alarm system; 
and
    (2) The incident response plan must describe procedures for how the 
entity will notify the appropriate Federal, State, or local law 
enforcement agencies of suspicious activity that may be criminal in 
nature and related to the entity, its personnel, or its select agents 
or toxins.
* * * * *

0
14. Section 73.15 is revised to read as follows:


Sec.  73.15  Training.

    (a) An individual or entity required to register under this part 
must provide information and training on biosafety, security (including 
security awareness), and incident response to:
    (1) Each individual with access approval from the HHS Secretary or 
Administrator before that individual has such access to select agents 
and toxins. The training must address the particular needs of the 
individual, the work they will do, and the risks posed by the select 
agents or toxins; and

[[Page 61115]]

    (2) Each individual not approved for access to select agents and 
toxins by the HHS Secretary or Administrator before that individual 
enters areas where select agents or toxins are handled or stored (e.g., 
laboratories, growth chambers, animal rooms, greenhouses, storage 
areas, shipping/receiving areas, production facilities, etc.). Training 
for escorted personnel must be based on the risk associated with 
accessing areas where select agents and toxins are used and/or stored.
    (b) Entities with Tier 1 select agents and toxins must conduct 
annual insider threat awareness briefings on how to identify and report 
suspicious behaviors.
    (c) Refresher training must be provided annually for individuals 
with access approval from the HHS Secretary or Administrator or at such 
time as the registered individual or entity significantly amends its 
security, incident response, or biosafety plans.
    (d) The Responsible Official must ensure a record of the training 
provided to each individual with access to select agents and toxins and 
each escorted individual (e.g., laboratory workers, visitors, etc.) is 
maintained. The record must include the name of the individual, the 
date of the training, a description of the training provided, and the 
means used to verify that the employee understood the training.

0
15. Section 73.16 is amended as follows:
0
a. By redesignating paragraphs (f), (g), (h), and (i) as paragraphs 
(i),(j), (k), and (g) respectively.
0
b. In newly redesignated paragraph (g), by removing the words 
``packaging and''.
0
c. By adding a new paragraph (f) to read as set forth below.
0
d. By adding a new paragraph (h) to read as set forth below.
0
e. By adding a new paragraph (l) to read as set forth below.


Sec.  73.16  Transfers.

* * * * *
    (f) After authorization is provided by APHIS or CDC, the packaging 
of the select agent(s) and toxin(s) is performed by an individual 
approved by the HHS Secretary or Administrator to have access to select 
agents and toxins and is in compliance with all applicable laws 
concerning packaging.
* * * * *
    (h) Transportation in commerce starts when the select agent(s) or 
toxin(s) are packaged for shipment and ready for receipt by a courier 
transporting select agent(s) or toxin(s) and ends when the package is 
received by the intended recipient who is an individual approved by the 
HHS Secretary or Administrator to have access to select agents and 
toxins, following a security risk assessment by the Attorney General.
* * * * *
    (l) A registered individual or entity transferring an amount of a 
HHS toxin otherwise excluded under the provisions of Sec.  73.3(d) 
must:
    (1) Transfer the amounts only after the transferor uses due 
diligence and documents that the recipient has a legitimate need (i.e., 
reasonably justified by a prophylactic, protective, bona fide research, 
or other peaceful purpose) to handle or use such toxins.
    (2) Report to CDC if they detect a known or suspected violation of 
Federal law or become aware of suspicious activity related to a toxin 
listed in Sec.  73.3(d) of this part.

0
16. Section 73.17 is amended as follows:
0
a. By revising paragraph (a)(1) introductory text to read as set forth 
below.
0
b. By redesignating paragraphs (a)(2) through (a)(6) as paragraphs 
(a)(3) through (a)(7) respectively.
0
c. By adding a new paragraph (a)(2) to read as set forth below.


Sec.  73.17  Records.

    (a) * * *
    (1) An accurate, current inventory for each select agent (including 
viral genetic elements, recombinant and/or synthetic nucleic acids, and 
organisms containing recombinant and/or synthetic nucleic acids) held 
in long-term storage (placement in a system designed to ensure 
viability for future use, such as in a freezer or lyophilized 
materials), including:
* * * * *
    (2) An accurate, current accounting of any animals or plants 
intentionally or accidentally exposed to or infected with a select 
agent (including number and species, location, and appropriate 
disposition);
* * * * *

0
17. Section 73.20 is revised to read as set forth below.


Sec.  73.20  Administrative review.

    (a) An individual or entity may appeal a denial, revocation, or 
suspension of registration under this part. The appeal must be in 
writing, state the factual basis for the appeal, and be submitted to 
the HHS Secretary within 30 calendar days of the decision.
    (b) An individual may appeal a denial, limitation, or revocation of 
access approval under this part. The appeal must be in writing, state 
the factual basis for the appeal, and be submitted to the HHS Secretary 
within 180 calendar days of the decision.
    (c) The HHS Secretary's decision constitutes final agency action.

[FR Doc. 2012-24389 Filed 10-2-12; 11:15 am]
BILLING CODE 4163-18-P