80 FR 42079 - Possession, Use, and Transfer of Select Agents and Toxins; Addition of Certain Influenza Virus Strains to the List of Select Agents and Toxins

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Federal Register Volume 80, Issue 136 (July 16, 2015)

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.

[Federal Register Volume 80, Number 136 (Thursday, July 16, 2015)]
[Proposed Rules]
[Pages 42079-42084]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-17435]


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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.

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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

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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