[Federal Register Volume 80, Number 136 (Thursday, July 16, 2015)]
[Proposed Rules]
[Pages 42079-42084]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-17435]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Part 73
[Docket No. CDC-2015-0050]
RIN 0920-AA58
Possession, Use, and Transfer of Select Agents and Toxins;
Addition of Certain Influenza Virus Strains to the List of Select
Agents and Toxins
AGENCY: Centers for Disease Control and Prevention, Department of
Health and Human Services.
ACTION: Notice of proposed rulemaking and request for comments.
-----------------------------------------------------------------------
SUMMARY: The Centers for Disease Control and Prevention (CDC) within
the Department of Health and Human Services (HHS) is proposing to add
certain influenza virus strains to the list of HHS select agents and
toxins. Specifically, we are proposing to add the influenza viruses
that contain the hemagglutinin (HA) from the Goose Guangdong/1/96
lineage (the influenza viruses that contain the hemagglutinin (HA) from
the A/Gs/Gd/1/96 lineage), including wild-type viruses, as a non-Tier 1
select agent. We are also proposing to add any influenza viruses that
contain the HA from the A/Gs/Gd/1/96 lineage that were made
transmissible among mammals by respiratory droplets in a laboratory as
a Tier 1 select agent. We have determined that these influenza viruses
have the potential to pose a severe threat to public health and safety.
DATES: Comments should be received on or before September 14, 2015.
ADDRESSES: You may submit comments, identified by Regulatory
Information Number (RIN), 0920-AA58 or Docket No. CDC-2015-0050 in the
heading of this document by any of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Mail: Division of Select Agents and Toxins, Centers for
Disease Control and Prevention, 1600 Clifton Road NE., Mailstop A-46,
Atlanta, Georgia 30329, ATTN: RIN 0920-AA58.
Instructions: All submissions received must include the agency name
and RIN for this rulemaking. All relevant comments received will be
posted without change to http://www.regulations.gov, including any
personal information provided.
Docket Access: For access to the docket to read background
documents or comments received or to download an electronic version of
the NPRM, go to http://www.regulations.gov. Comments will be available
for public inspection Monday through Friday, except for legal holidays,
from 9 a.m. until 5 p.m. at 1600 Clifton Road NE., Atlanta, GA 30329.
Please call ahead to 1-866-694-4867 and ask for a representative in the
Division of Select Agents and Toxins to schedule your visit. Our
general policy for comments and other submissions from members of the
public is to make these submissions available for public viewing on the
Internet as they are received and without change.
[[Page 42080]]
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 30329.
Telephone: (404) 718-2000.
SUPPLEMENTARY INFORMATION: The preamble to this notice of proposed
rulemaking is organized as follows:
I. Public Participation
II. Background
A. Historical Background for This Proposed Rulemaking
B. Legal Authorities
III. Alternatives Considered
IV. Regulatory Analyses
A. Executive Order 12866 and 13563
B. Regulatory Flexibility Act
C. Paperwork Reduction Act
D. Executive Order 12988: Civil Justice Reform
E. Executive Order 13132: Federalism
F. Plain Writing Act of 2010
V. References
I. Public Participation
Interested persons or organizations are invited to participate in
this rulemaking by submitting written views, recommendations, and data.
We are establishing a docket to provide an opportunity for interested
persons to submit comments, research data, and other information that
will better inform us about the effect the regulation of these two
viruses will have. Comments are invited on any topic related to this
rulemaking, but in particular, we welcome comment on the following
questions:
(1) Are there any vaccine candidates that include the HA from the
A/Gs/Gd/1/96 lineage that should be considered for an exclusion from
the regulation?
(2) What are the criteria that could be used for exclusion of
attenuated strains which could include vaccine candidates?
(3) What criteria or experimental conditions should be considered
in defining transmissibility among mammals via respiratory droplets?
(4) What criteria or experimental conditions should be used to
define an appropriate mammalian model of influenza transmission?
(5) What is the impact of designating as a Tier 1 select agent any
influenza virus that contains the HA from the A/Gs/Gd/1/96 lineage that
was made transmissible among mammals by respiratory droplets in the
laboratory?
(6) Is the potential for influenza A H5 viruses that contain the HA
from the A/Gs/Gd/1/96 lineage to be a low pathogenic avian influenza
(LPAI) (by design or nature) but still pose a severe threat to public
health and safety significant enough to regulate as a select agent?
II. Background
A. Historical Background for This Proposed Rulemaking
Since late 2003, the World Health Organization (WHO) has reported
over 600 cases of human infection with highly pathogenic avian
influenza (HPAI) H5N1 viruses with a mortality rate that exceeds 50
percent in hospitalized patients (Ref 1). Current epidemiologic
evidence indicates that, once transmitted into a human host, H5N1
viruses may result in more severe disease in humans than other subtypes
of influenza.
One important factor that can account for some of the increased
pathogenicity is the hemagglutinin (HA) molecule. Cleavage of the HA
molecule by host proteases (enzymes that can break amino acid bonds)
enables influenza viruses to productively infect cells (i.e.,
replicate). For human influenza viruses, replication is generally
restricted to the respiratory tract. However, HPAI H5N1 viruses contain
a polybasic amino acid sequence in the HA molecule that is not found in
human influenza viruses. This feature allows the molecule to be cleaved
by a wider variety of proteases throughout the body.
Extrapulmonary dissemination of HPAI H5N1 virus has been documented
among some fatal human HPAI H5N1 virus infections. The HA molecule
mediates binding of the influenza virus to host cells in the
respiratory tract. Human influenza viruses preferentially bind to
different receptors than avian influenza viruses (Ref 2). While human
influenza virus receptors are more prevalent in the upper respiratory
tract, the receptors that bind avian viruses are present in the lower
respiratory tract of humans. The ability of H5N1 viruses to bind and
infect cells within the lung may contribute to the severity of H5N1
induced viral pneumonia (Ref 3-5). Furthermore, a change from avian- to
human-type receptor-binding specificity, as seen with the pandemic
strains of 1918 (H1N1), 1957 (H2N2), and 1968 (H3N2), is thought to be
a critical step in the adaptation of avian influenza viruses to humans
and the ability to transmit efficiently among humans (Ref 6-8). In two
independent studies (Ref 9-10), investigators have shown that
laboratory modified HPAI H5N1 influenza viruses with certain mutations
can be transmitted via the respiratory route between ferrets. Ferrets
are widely considered to provide the best animal model for exploring
these aspects of influenza virus pathogenicity as they might relate to
human infection (Ref 11).
We recognize that all HPAI H5N1 influenza virus HA clades found in
humans to date descended from the A/Gs/Gd/1/96 HA lineage (Ref 12).
Currently, all HPAI H5 subtype viruses are regulated by the U.S.
Department of Agriculture (USDA) Animal and Plant Health Inspection
Service (APHIS) whose oversight focuses on the threat to animal health.
We conclude that (1) designating as a non-Tier 1 HHS select agent any
influenza viruses that contain an HA from the A/Gs/Gd/1/96 lineage and
(2) designating as a Tier 1 HHS select agent any influenza viruses that
contain the HA from the A/Gs/Gd/1/96 lineage that were made
transmissible among mammals by respiratory droplets in a laboratory,
will expand the regulatory oversight of this agent to address the
potential threat of these viruses to human health. We conclude this
expanded oversight is needed because while the USDA required biosafety
measures for the HPAI H5 subtype viruses may also be generally
beneficial to public health; their regulatory oversight is focused
primarily on risks to agricultural animals rather than direct effects
on human health.
According to Federal government influenza subject matter experts,
it is possible for an influenza virus that contains the HA from the A/
Gs/Gd/1/96 lineage to be classified as LPAI, and therefore not be
regulated as a select agent by USDA, but still be capable of causing
severe disease in humans. Designating these viruses as HHS select
agents will ensure that influenza strains with the greatest potential
for major direct effects on human health will be regulated with a focus
on protection of human health. This approach would include LPAI viruses
with the polybasic amino acid sequence removed from the HA molecule
that may not pose a severe threat to avian species but could pose a
severe threat to public health and safety.
Whether the (1) influenza viruses that contain an HA from the A/Gs/
Gd/1/96 lineage and (2) influenza viruses that contain the HA from the
A/Gs/Gd/1/96 lineage that were made transmissible among mammals by
respiratory droplets in a laboratory should be regulated as a HHS
select agent was considered by HHS/CDC's Intragovernmental Select
Agents and Toxins Technical Advisory Committee (ISATTAC). The ISATTAC
is comprised of Federal government scientists from HHS/CDC, the
Biomedical Advanced Research and Development Authority (BARDA) within
the Office of the Assistant Secretary for Preparedness and Response
(HHS/ASPR) in HHS, the
[[Page 42081]]
National Institutes of Health (HHS/NIH), the Food and Drug
Administration (HHS/FDA), USDA/APHIS, the USDA/Agricultural Research
Service, the USDA/Center for Veterinary Biologics, the Department of
Homeland Security, and the Department of Defense. The criteria used by
the ISATTAC in its review were the degree of pathogenicity,
communicability, ease of dissemination, route of exposure,
environmental stability, ease of production, ability to genetically
manipulate or alter, long-term health effects, acute morbidity, acute
mortality, available treatment, status of host immunity, vulnerability
of special populations, and the burden or impact on the health care
system. The ISATTAC recommended that (1) the influenza viruses
containing an HA from the A/Gs/Gd/1/96 lineage should be regulated as
an HHS select agent (non-Tier 1), and (2) the influenza viruses that
contain the HA from the A/Gs/Gd/1/96 lineage that were made
transmissible among mammals by respiratory droplets in a laboratory
should be regulated as a Tier 1 HHS select agent. In making its
recommendations, the ISATTAC considered both the historical data
regarding the A/Gs/Gd/1/96 lineage and data from current in vitro and
in vivo animal studies. The virulence of viruses of this lineage, the
data showing transmissibility of genetically modified H5N1 viruses
among ferrets, together with the fact that the level of immunity in the
general population is low, were all considered. In addition, the
ISATTAC recommended limiting the Tier 1 status to only those viruses
that were made transmissible among mammals by respiratory droplets.
Transmission by respiratory droplets would be the most similar route to
normal human-to-human transmission, as opposed to transmission by other
respiratory routes such as intra nasal exposure which is not a normal
route of human infection. In addition, the ISATTAC voiced concern that
an influenza pandemic caused by viruses containing an HA from the A/Gs/
Gd/1/96 lineage, could potentially overwhelm the health care system.
On July 2, 2010, the President signed Executive Order 13546,
``Optimizing the Security of Biological Select Agents and Toxins in the
United States'' that directed the Secretaries of HHS and USDA 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. Executive Order
13546 also established the Federal Experts Security Advisory Panel
(FESAP) to advise the HHS and USDA Secretaries on the designation of
Tier 1 agents and toxins. In December of 2010, the FESAP provided
recommendations on the composition of the HHS and USDA select agent and
toxin lists, including a subset of agents and toxins recommended for
Tier 1 designation.
In accordance with Executive Order 13546, HHS/CDC published a final
rule (77 FR 61084) on October 5, 2012 which 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 and ongoing suitability assessments 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.
On October 17, 2012, HHS/CDC published a request for information
and comment (RFI) (77 FR 63783) to provide an opportunity for
interested persons to submit comments, research data, and other
information to better inform us about the risk to public health and
safety posed by HPAI H5N1 influenza viruses containing the HA from the
A/Gs/Gd/1/96 lineage.
We received responses from thirty-one commenters associated with
academic, private and commercial institutions and professional
societies. The majority of the commenters addressed the specific
questions found in the request for information.
Twenty-seven of the thirty-one commenters asserted that influenza
viruses of this lineage (1) exhibit high lethality in humans (exceeds
50% mortality rate, (Ref 1), (2) exhibit efficient aerosol
transmissibility and retention of virulence in mammals following
experimental adaptation to mammals in a laboratory setting, and (3)
potentially may acquire efficient aerosol transmissibility in mammals
and retention of virulence through natural adaptation to mammals in
nature. The commenters concluded that HPAI H5N1 influenza viruses
containing the HA from the Goose/Guangdong/1/96 lineage pose a severe
threat to public health and safety and warrant regulation as HHS select
agents. One commenter stated that listing these viruses as HHS select
agents would ``enable the regulatory process to evaluate, and to
respond to, impacts on human health as well as impacts on
agriculture.''
Twenty commenters also stated that HPAI H5N1 viruses that contain
the HA from the A/Gs/Gd/1/96 lineage should not be designated as Tier 1
agents. The commenters believed that select agent biosafety and
security requirements currently in place in regards to HPAI are
adequate to protect against a release (accidental or intentional) or
theft (13). However, some commenters also stated that any laboratory
generated influenza viruses that contain the hemagglutinin (HA) from
the A/Gs/Gd/1/96 lineage that are mammalian transmissible by the
respiratory route should be regulated as a Tier 1 HHS select agent due
to the combination of (1) high human virulence (presumed from that of
their precursors), (2) potentially high human-to-human
transmissibility, (3) nonexistence in the wild, and (4) lack of
adequate control measures to contain its spread if released in the
environment. The same twenty commenters felt that the mammalian-
transmissible H5N1 strains are a unique or nearly unique threat to
public health and therefore warrant Tier 1 status.
HHS/CDC also asked if there were other influenza strains containing
HA from Goose/Guangdong/1/96 lineage that would pose a severe threat to
public health and safety. None of the commenters was aware of any other
strains that would pose a severe threat to public health and safety.
HHS/CDC asked if special precautions (i.e., safety and containment
measures) should be considered when working with diagnostic specimens
suspected of containing HPAI H5N1 influenza viruses containing the HA
from the A/Gs/Gd/1/96 lineage (i.e., any precautions versus none at
all, precautions beyond those usual for clinical samples and/or
laboratory microbes, etc.). The commenters varied on their
recommendations. Some commenters recommended that diagnostic work with
this virus should be performed in BSL-3 laboratories. Other commenters
recommended that diagnostic work be carried out in BSL-2 facility with
special precautions (face masks, etc.) or in an enhanced BSL-2
facility, which would include performing all open container work and
aerosol-producing procedures in a Class II biological safety cabinet.
HHS/CDC asked if special precautions (i.e., safety and containment
measures) should be considered when working with strains of HPAI
containing the HA from the A/Gs/Gd/1/96 lineage that have been shown to
be transmissible between mammals beyond those
[[Page 42082]]
recommended for non-mammalian transmissible strains. The commenters
varied on their recommendations. Commenters recommended that work with
mammalian aerosol-transmissible H5N1 strains should be performed only
using the highest physical containment and operational procedures
(i.e., BSL-4 containment and procedures) and only after an open,
transparent, and independent process of risk-benefit assessment and
risk mitigation. Some commenters recommended that work with diagnostic
specimens suspected of containing mammalian-transmissible H5N1 virus
should be treated under BSL-3+ or BSL-4 conditions where possible (and
consistent with the need for rapid diagnosis), and in any case should
be handled only by individuals with training and experience with high-
containment pathogens. Some commenters recommended that H5N1
vaccination of those working with transmissible H5N1 viruses should
probably be required, but an increase in containment level is not
necessary.
HHS/CDC, with advice from the ISATTAC and from public input
received in response to the RFI, published in CDC's Morbidity and
Mortality Weekly Report (MMWR) (June 28, 2013/62(RR06);1-7) Biosafety
Guidelines for Working with Influenza Viruses Containing an HA from the
A/goose/Guangdong/1/96 lineage which can be found at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6206a1.htm?s_cid=rr6206a1_w.
Based on the public comments to the RFI and in consultation with
the ISATTAC, we are proposing a tiered approach to the regulation of
influenza viruses containing the HA from the A/Gs/Gd/1/96 lineage.
Under our proposal, influenza viruses that contain the HA from the A/
Gs/Gd/1/96 lineage, including wild-type and laboratory-derived viruses,
will be regulated as a non-Tier 1 select agent. This designation
recognizes the public health threat posed by the high mortality rate,
lack of a readily available vaccine, and the absence of immunity in the
population. The USDA regulates avian influenza virus, although the USDA
regulations exclude any ``low pathogenic strains of avian influenza
virus . . . provided that the individual or entity can identify that
the agent is within the exclusion category'' (Ref 13). Accordingly, all
reported human infections with influenza viruses containing the HA from
the A/Gs/Gd/1/96 lineage are considered to be HPAI by the USDA and
therefore are regulated as select agents by USDA. However, influenza
subject matter experts have indicated that there is a possibility that
influenza viruses that contain the HA from the A/Gs/Gd/1/96 lineage
could be classified as LPAI, as a result of mutation or genetic
manipulation and yet cause severe disease in humans. Under the current
paradigm, these strains would not be regulated as select agents. Our
regulatory strategy would address this potential gap in select agent
oversight. We do not anticipate this listing to have a significant
impact on the select agent stakeholder community as most entities
working with this agent are already registered to work with select
agents.
We are also proposing the regulation as a Tier 1 HHS select agent
influenza viruses that contain the HA from the A/Gs/Gd/1/96 lineage
that were made transmissible among mammals by respiratory droplets in a
laboratory. Designating these viruses as Tier 1 recognizes the higher
public health risk posed by these viruses and establishes security
requirements above those currently proscribed by the USDA for HPAI.
This strategy also recognizes that HHS considers these types of
experiments with these viruses to be of a significant public health
concern and is consistent with recent United States Government policy
regarding dual use research of concern and gain-of-function research,
and the framework for ``Guiding US HHS Funding Decisions about Research
Proposals with the Potential for Generating Highly Pathogenic Avian
Influenza H5N1 Viruses that are Transmissible among Mammals by
Respiratory Droplets'' (February 2013); and therefore warranting
increased oversight (Ref 14-16). Designating these agents as HHS select
agents also addresses a potential gap in current select agent oversight
since laboratory-generated viruses that are capable of causing human
disease do not necessarily have to be HPAI.
We recognize that this new regulatory paradigm could have
implications on the development of vaccines needed during an influenza
outbreak in the human population. We understand the importance of
vaccine development and availability. Accordingly, we are seeking
comments on how to best accommodate the need of vaccine development
while protecting the public health and safety from the accidental or
intentional release of these viruses. We are interested in receiving
comments on criteria that could be used for the exclusion of vaccine
reassortants such as those well-characterized vaccine strains or
backbones (e.g., PR8) that have been demonstrated to not pose a severe
threat to public health and safety.
B. Legal Authorities
The Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (Bioterrorism Response Act) requires the HHS
Secretary to establish by regulation a list of biological agents and
toxins that have the potential to pose a severe threat to public health
and safety. In determining whether to include an agent or toxin on the
list, the HHS Secretary considers criteria such as the effect on human
health of exposure to an agent or toxin; the degree of contagiousness
of the agent and the methods by which the agent or toxin is transferred
to humans; the availability and effectiveness of pharmacotherapies and
immunizations to treat and prevent illnesses resulting from an agent or
toxin; and the needs of children and other vulnerable populations. The
current list of HHS select agents and toxins can be found at 42 CFR
73.3 (HHS select agents and toxins) and 42 CFR 73.4 (Overlap select
agents and toxins). The list of HHS and Overlap select agents and
toxins is available at: http://www.selectagents.gov/SelectAgentsandToxinsList.html.
III. Alternatives Considered
After we published the request for information and comment (RFI)
(77 FR 63783) on October 17, 2012, we reviewed all comments received
regarding the risk to public health and safety posed by HPAI H5N1
influenza viruses containing the HA from the A/Gs/Gd/1/96 lineage. Even
though all HPAI H5 subtype viruses are regulated by USDA/APHIS, whose
oversight focuses on the threat to animal health, the majority of
commenters believed that HPAI H5N1 influenza viruses containing the HA
from the Goose/Guangdong/1/96 lineage pose a severe threat to public
health and safety and warrant regulation as HHS select agent. Given the
recent research that has identified specific determinants of
transmission for H5N1 influenza viruses in ferrets, we conclude that
listing influenza viruses that contain an HA from the A/Gs/Gd/1/96
lineage as an HHS select agent would allow us to focus on biosafety
measures that would mitigate the risk to public health and safety.
In researching the proposed change, we also reviewed how USDA/APHIS
designated the avian influenza virus (highly pathogenic) as a non-Tier
1 agent. We conclude that (1) listing influenza viruses that contain an
HA from the A/Gs/Gd/1/96 lineage as a non-Tier 1 HHS select agent and
(2) listing any influenza viruses that contain the
[[Page 42083]]
HA from the A/Gs/Gd/1/96 lineage that were made transmissible among
mammals by respiratory droplets in a laboratory as a Tier 1 HHS select
agent, will ensure that the regulatory oversight of this agent will
expand to include the potential threat of these viruses to human
health.
III. Regulatory Analyses
A. Executive Orders 12866 and 13563
Executive Orders 12866 (Regulatory Planning and Review) and 13563
(Improving Regulation and Regulatory Review) 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). E.O.
13563 emphasizes the importance of quantifying both costs and benefits,
of reducing costs, of harmonizing rules, and of promoting flexibility.
Under E.O. 12866 HHS must determine whether a regulatory action is
``significant.'' A ``significant regulatory action'' under E.O. 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.
Based on a literature and database search, the current possessors
are academic and government institutions. As such, we conclude that the
majority of the viruses that will be regulated by HHS are already
regulated by USDA. If it is determined that there are unregistered
possessors of the agent as a result of the comments received from this
proposed rule, we will include a grace period to allow these
individuals to become compliant with the regulations prior to the full
implementation. As a result of the search, we conclude that the
addition of influenza viruses that contain an HA from the A/Gs/Gd/1/96
lineage to the HHS select agent list will not 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. We also believe that this change will not
create a serious inconsistency or otherwise interferes with an action
taken or planned by another agency; materially alters the budgetary
impact of entitlements, grants, user fees or loan programs or the
rights and obligations of recipients; or raises novel legal or policy
issues. However, we would be interested in receiving any information
from the public on the potential for an economic impact that might
result from this proposal.
B. Regulatory Flexibility Act
We are continuing to assess the potential economic effects of this
action on small entities, but based on a literature and database search
that the current possessors are academic and government institutions,
we conclude that this proposed rule will not have a significant
economic impact on a substantial number of small entities.
C. Paperwork Reduction Act
In accordance with section 3507(d) of the Paperwork Reduction Act
of 1995 (44 U.S.C. 3501 et seq.), the information collection and/or
recordkeeping requirements included in this proposed rule have been
approved by the Office of Management and Budget (OMB) under OMB control
number 0920-0576 (expiration November 30, 2015).
Please send written comments on the new information collection
contained in this proposed rule or requests for a copy of the data
collection to Leroy A. Richardson, 1600 Clifton Road, MS-D74, Atlanta,
GA 30329 or send an email to [email protected].
Based on a literature and database search, the current possessors
are academic and government institutions and are already regulated by
USDA. Since entities who possess influenza viruses that contain an HA
from the A/Gs/Gd/1/96 lineage and are HPAI are already regulated by
USDA/APHIS, the proposed rule will require an entity to make an
amendment to its registration with the Federal Select Agent Program
using relevant portions of APHIS/CDC Form 1 (Application for
Registration for Possession, Use, and Transfer of Select Agents and
Toxins) to indicate the registration for the viruses regulated by HHS.
Estimated time to amend this form is 45 minutes for one select agent.
Since this agent is currently regulated by USDA/APHIS, we conclude that
there is no increase in the number of respondents.
D. Executive Order 12988: Civil Justice Reform
This proposed rule has been reviewed under Executive Order 12988,
Civil Justice Reform. This proposed rule: (1) Preempts all State and
local laws and regulations that are inconsistent with this rulemaking;
(2) has no retroactive effect; and (3) does not require administrative
proceedings before parties may file suit in court challenging this
rule.
E. Executive Order 13132: Federalism
This proposed rule has been reviewed under E.O. 13132, Federalism.
The document does not propose any regulation that would expressly
preempt State, local, and Indian Tribe requirements, or that would have
any substantial direct effects on the States, or on the distribution of
power and responsibilities among the various levels of government.
F. Plain Writing Act of 2010
Under Public Law 111-274 (October 13, 2010), executive branch
Departments and Agencies are required to use ``clear Government
communication that the public can understand and use.'' E.O. 13563
(Improving Regulation and Regulatory Review) states that ``[our
regulatory system] must ensure that regulations are accessible,
consistent, written in plain language, and easy to understand.'' HHS
has attempted to use plain language in writing this proposed rule and
seek comment from the public on our attempt to use plain language in
this rulemaking.
V. References
1. WHO, Cumulative number of confirmed human cases for avian
influenza A(H5N1) reported to WHO, 2003-2011; http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/index.html.
2. Fukuyama S, Kawaoka Y. The pathogenesis of influenza virus
infections: the contributions of virus and host factors. Current
Opinions Immunology. 2011 Aug; 23(4):481-6. Epub 2011 Aug 11.
3. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Avian
flu: influenza virus receptors in the human airway. Nature. 2006 Mar
23; 440(7083):435-6.
4. Nicholls JM, Chan MC, Chan WY, Wong HK, Cheung CY, Kwong DL, Wong
MP, Chui WH, Poon LL, Tsao SW., Guan Y, Peiris JS. Tropism of avian
influenza A (H5N1) in the upper and lower respiratory tract. Nature
Medicine. 2007 Feb; 13(2):147-9. Epub 2007 Jan 7.
5. Van Riel D, Munster VJ, de Wit E, Rimmelzwaan GF, Fouchier RA,
Osterhaus AD, Kuiken T. H5N1 Virus
[[Page 42084]]
Attachment to Lower Respiratory Tract. Science. 2006 Apr 21;
312(5772):399. Epub 2006 Mar 23.
6. Matrosovich M, Tuzikiv A, Bovin N, Gambaryan A, Klimov A,
Castrucci MR, Donatelli I, Kawaoka Y. Early alterations of the
receptor-binding properties of H1, H2, and H3 avian influenza virus
hemagglutinins after their introduction into mammals. J Virology.
2000 Sept; 74 (18):8502-8512.
7. Stevens J, Blixt O, Glaser L, Taubenberger J, Palese P, Paulson
JC, Wilson I.A. Glycan microarray analysis of the hemagglutinins
from modern and pandemic influenza viruses reveals different
receptor specificities. J Molecular Biology. 2006 Feb 3; 355(5):
1143-1155.
8. Connor, RJ, Kawaoka, Y, Webster, RG, Paulson, JC. Receptor
specificity in human, avian, and equine H2 and H3 influenza virus
isolates. Virology. 1994 Nov 15;205(1):17-23.
9. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G,
Hanson A, Katsura H, Watanabe S, Li C, Kawakami E, Yamada S, Kiso M,
Suzuki Y, Maher EA, Neumann G, Kawaoka Y. Experimental adaptation of
an influenza H5 HA confers respiratory droplet transmission to a
reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012 May 2;
486(7403):420-8.
10. Russell CA, Fonville JM, Brown AE, Burke DF, Smith DL, James SL,
Herfst S, van Boheemen S, Linster M, Schrauwen EJ, Katzelnick L,
Moster[iacute]n A, Kuiken T, Maher E, Neumann G, Osterhaus AD,
Kawaoka Y, Fouchier RA, Smith DJ. The potential for respiratory
droplet-transmissible A/H5N1 influenza virus to evolve in a
mammalian host. Science. 2012 Jun 22; 336(6088):1541-7.
11. Belser JA, Szretter KJ, Katz JM, Tumpey TM. Use of animal models
to understand the pandemic potential of highly pathogenic avian
influenza viruses. Adv Virus Research. 2009;73:55-97.
12. Wan, XF. Lessons from Emergence of A/Goose/Guangdong/1996-Like
H5N1 Highly Pathogenic Avian Influenza Viruses and Recent Influenza
Surveillance Efforts in Southern China. Zoonoses Public Health. 2012
Sep;59 Suppl 2:32-42. doi: 10.1111/j.1863-2378.2012.01497.x.
13. Title 9: Animals and Animal Products, Part 121--Possession, Use,
And Transfer Of Select Agents And Toxins. Available at http://www.ecfr.gov/cgi-bin/retrieveECFR?gp=1&SID=b9126e9fba23e3e7933354a1d2630d72&ty=HTML&h=L&n=9y1.0.1.5.58&r=PART.
14. United States Government Policy for Oversight of Life Sciences
Dual Use Research of Concern (March 29, 2012) http://www.phe.gov/s3/dualuse/Documents/us-policy-durc-032812.pdf.
15. A Framework for Guiding U.S. Department of Health and Human
Services Funding Decisions about Research Proposals with the
Potential for Generating Highly Pathogenic Avian Influenza H5N1
Viruses that are Transmissible among Mammals by Respiratory Droplets
http://www.phe.gov/s3/dualuse/Documents/funding-hpai-h5n1.pdf.
United States Government Policy for Institutional Oversight of Life
Sciences Dual Use Research of Concern (http://www.phe.gov/s3/dualuse/Documents/oversight-durc.pdf).
List of Subjects
Biologics, Influenza viruses, Packaging and containers, Penalties,
Select agents and toxins, Reporting and recordkeeping requirements,
Transportation.
For the reasons stated in the preamble, the Centers for Disease
Control and Prevention, U.S. Department of Health and Human Services,
proposes to amend 42 CFR part 73, as follows:
PART 73 [AMENDED]
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 two entries to the list in paragraph (b) of Sec. 73.3 to read
as follows:
Sec. 73.3 HHS select agents and toxins.
* * * * *
(b) * * *
Influenza viruses that contain the hemagglutinin (HA) from the
Goose Guangdong/1/96 lineage,
Any laboratory generated Influenza viruses that contain the
hemagglutinin (HA) from the A/Goose Guangdong/1/96 lineage that are
mammalian transmissible by the respiratory route *
* * * * *
Dated: July 8, 2015.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2015-17435 Filed 7-15-15; 8:45 am]
BILLING CODE 4163-18-P