National Institutes of Health (NIH) Office of Science Policy (OSP): Proposed Changes to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), 54332-54340 [2023-17178]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES
• National Institutes of Health

[Federal Register Volume 88, Number 153 (Thursday, August 10, 2023)]
[Notices]
[Pages 54332-54340]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-17178]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Institutes of Health (NIH) Office of Science Policy 
(OSP): Proposed Changes to the NIH Guidelines for Research Involving 
Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines)

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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SUMMARY: The National Institutes of Health (NIH) seeks input on a 
proposal to revise the NIH Guidelines for Research Involving 
Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) to 
include specific considerations and requirements for conducting 
research involving gene drive modified organisms (GDMO) in contained 
research settings. NIH is proposing to update the NIH Guidelines to 
clarify minimum containment requirements, propose considerations for 
performing risk assessments, and define additional institutional 
responsibilities regarding Institutional Biosafety Committees (IBCs) 
and Biosafety Officers (BSOs). The proposed revisions are specific to 
GDMO research subject to the NIH Guidelines, conducted in contained 
settings and are consistent with the recommendations of

[[Page 54333]]

the NIH Novel and Exceptional Technology Research Advisory Committee 
report, Gene Drives in Biomedical Research (NExTRAC Report). NIH does 
not currently support research involving potential field release of 
GDMOs and the NIH Guidelines pertain to contained research; 
accordingly, no changes regarding potential field release are being 
proposed in this Notice. NIH is also proposing revisions to the NIH 
Guidelines to harmonize with the Biosafety in Microbiological and 
Biomedical Laboratories (BMBL), 6th edition regarding the Risk Group 
(RG) categorization of West Nile Virus (WNV) and Saint Louis 
Encephalitis Virus (SLEV).

DATES: To ensure consideration, comments must be submitted in writing 
by October 10, 2023.

ADDRESSES: Comments may be submitted electronically to https://osp.od.nih.gov/proposed-amendments-to-the-nih-guidelines-for-research-involving-recombinant-or-synthetic-nucleic-acid-molecules-nih-guidelines/. Comments are voluntary and may be submitted anonymously. 
You may also voluntarily include your name and contact information with 
your response. Other than your name and contact information, please do 
not include in the response any personally identifiable information or 
any information that you do not wish to make public. Proprietary, 
classified, confidential, or sensitive information should not be 
included in your response. After the Office of Science Policy (OSP) has 
finished reviewing the responses, the responses may be posted to the 
OSP website without redaction.

FOR FURTHER INFORMATION CONTACT: Caroline Young, ScM, Acting Director 
of the Division of Biosafety, Biosecurity, and Emerging Biotechnology 
Policy, Office of Science Policy, at (301) 496-9838 or 
[email protected].

SUPPLEMENTARY INFORMATION: The NIH currently supports basic gene drive 
research in contained laboratory settings as the technology holds great 
promise for advancing public health, particularly through the potential 
to reduce transmission of vector-borne human diseases such as malaria, 
dengue, or Zika. Under certain conditions, gene drive technology 
enables researchers to promote the spread of certain genetic traits 
that has the potential to mitigate disease by driving traits through a 
specific species population at a faster rate with fewer reproductive 
cycles.
    Gene drive technology presents opportunities for many life sciences 
applications with potential benefits to public health, agriculture, and 
the environment but also raise biosafety, ethical, and social concerns. 
To help consider issues associated with conducting research involving 
GDMOs safely and responsibly, the NIH charged an advisory committee to 
the NIH Director, the Novel and Exceptional Technology and Research 
Advisory Committee (NExTRAC), to consider whether existing biosafety 
guidance is adequate for contained laboratory research utilizing GDMOs. 
The NExTRAC made multiple recommendations for strengthening NIH's 
existing policies and guidance, which were shared for public input and 
ultimately accepted by the NIH Director. These proposed changes only 
address the NExTRAC's recommendations pertaining to contained research. 
NIH does not currently support research involving potential field 
release of GDMOs and the NIH Guidelines pertain to contained research; 
as such, no changes are being proposed in this notice regarding field 
release research of GDMOs.
    NIH is seeking input on its proposal to amend the NIH Guidelines to 
ensure the continued responsible research involving GDMOs in contained 
research settings. Specifically, NIH proposes to:
    (1) clarify minimum containment requirements for research involving 
GDMOs;
    (2) propose considerations for risk assessment;
    (3) define additional institutional responsibilities for 
Institutional Biosafety Committees (IBCs) and Biosafety Officers 
(BSOs).
    In addition to the amendments proposed related to contained 
research involving GDMOs, the NIH is seeking input on its proposal to:
    1. replace the term ``helper viruses'' with the broader term 
``helper systems''; and
    2. reclassify WNV and SLEV as risk group 2 agents for consistency 
with containment guidance provided in the Biosafety in Microbiological 
and Biomedical Laboratories (BMBL), 6th edition.

Current Language and Proposed Amendments to the NIH Guidelines

    A definition for gene drive is proposed to be added to Section I-E, 
specifically:

Section I-E. General Definitions

    Section I-E-7. ``Gene drive'' is defined as a technology whereby a 
particular heritable element biases inheritance in its favor, resulting 
in the heritable element becoming more prevalent than predicted by 
Mendelian laws of inheritance in a population over successive 
generations.
    Section II-A-3, which provides guidance for conducting a 
comprehensive risk assessment, has been updated in the past to provide 
additional guidance regarding issues that should be considered for 
research involving emerging technologies (e.g., guidance for research 
with organisms involving synthetic nucleic acids when the parent 
organism is not obvious). Robust risk assessment for research with 
GDMOs may present challenges due to different or increased risks 
associated with the potential to persist and spread in the environment. 
To address some of these challenges, Section II-A-3 is proposed to be 
amended to include considerations for risk assessment.
    Section II-A-3 currently states:

Section II-A-3. Comprehensive Risk Assessment

    In deciding on the appropriate containment for an experiment, the 
first step is to assess the risk of the agent itself. Appendix B, 
Classification of Human Etiologic Agents on the Basis of Hazard, 
classifies agents into Risk Groups based on an assessment of their 
ability to cause disease in humans and the available treatments for 
such disease. Once the Risk Group of the agent is identified, this 
should be followed by a thorough consideration of how the agent is to 
be manipulated. Factors to be considered in determining the level of 
containment include agent factors such as: virulence, pathogenicity, 
infectious dose, environmental stability, route of spread, 
communicability, operations, quantity, availability of vaccine or 
treatment, and gene product effects such as toxicity, physiological 
activity, and allergenicity. Any strain that is known to be more 
hazardous than the parent (wild-type) strain should be considered for 
handling at a higher containment level. Certain attenuated strains or 
strains that have been demonstrated to have irreversibly lost known 
virulence factors may qualify for a reduction of the containment level 
compared to the Risk Group assigned to the parent strain (see Section 
V-B, Footnotes and References of Sections I-IV).
    While the starting point for the risk assessment is based on the 
identification of the Risk Group of the parent agent, as technology 
moves forward, it may be possible to develop an organism containing 
genetic sequences from multiple sources such that the parent agent may 
not be obvious. In such cases, the risk assessment should include at 
least two levels of analysis. The first involves a

[[Page 54334]]

consideration of the Risk Groups of the source(s) of the sequences and 
the second involves an assessment of the functions that may be encoded 
by these sequences (e.g., virulence or transmissibility). It may be 
prudent to first consider the highest Risk Group classification of all 
agents that are the source of sequences included in the construct. 
Other factors to be considered include the percentage of the genome 
contributed by each parent agent and the predicted function or intended 
purpose of each contributing sequence. The initial assumption should be 
that all sequences will function as they did in the original host 
context.
    The Principal Investigator and Institutional Biosafety Committee 
must also be cognizant that the combination of certain sequences in a 
new biological context may result in an organism whose risk profile 
could be higher than that of the contributing organisms or sequences. 
The synergistic function of these sequences may be one of the key 
attributes to consider in deciding whether a higher containment level 
is warranted, at least until further assessments can be carried out. A 
new biosafety risk may occur with an organism formed through 
combination of sequences from a number of organisms or due to the 
synergistic effect of combining transgenes that results in a new 
phenotype.
    A final assessment of risk based on these considerations is then 
used to set the appropriate containment conditions for the experiment 
(see Section II-B, Containment). The appropriate containment level may 
be equivalent to the Risk Group classification of the agent, or it may 
be raised or lowered as a result of the above considerations. The 
Institutional Biosafety Committee must approve the risk assessment and 
the biosafety containment level for recombinant or synthetic nucleic 
acid experiments described in Sections III-A, Experiments that Require 
NIH Director Approval and Institutional Biosafety Committee Approval, 
Before Initiation; III-B, Experiments that Require NIH OSP and 
Institutional Biosafety Committee Approval Before Initiation; III-C, 
Experiments Involving Human Gene Transfer that Require Institutional 
Biosafety Committee Approval Prior to Initiation; III-D, Experiments 
that Require Institutional Biosafety Committee Approval Before 
Initiation.
    Careful consideration should be given to the types of manipulation 
planned for some higher Risk Group agents. For example, the RG2 dengue 
viruses may be cultured under the Biosafety Level (BL) 2 containment 
(see Section II-B); however, when such agents are used for animal 
inoculation or transmission studies, a higher containment level is 
recommended. Similarly, RG3 agents such as Venezuelan equine 
encephalomyelitis and yellow fever viruses should be handled at a 
higher containment level for animal inoculation and transmission 
experiments.
    Individuals working with human immunodeficiency virus (HIV), 
hepatitis B virus (HBV) or other bloodborne pathogens should consult 
the applicable Occupational Safety and Health Administration (OSHA) 
(https://www.osha.gov/) (regulation, 29 CFR 1910.1030, and OSHA 
publication 3127 (1996 revised). BL2 containment is recommended for 
activities involving all blood-contaminated clinical specimens, body 
fluids, and tissues from all humans, or from HIV- or HBV-infected or 
inoculated laboratory animals. Activities such as the production of 
research-laboratory scale quantities of HIV or other bloodborne 
pathogens, manipulating concentrated virus preparations, or conducting 
procedures that may produce droplets or aerosols, are performed in a 
BL2 facility using the additional practices and containment equipment 
recommended for BL3. Activities involving industrial scale volumes or 
preparations of concentrated HIV are conducted in a BL3 facility, or 
BL3 Large Scale if appropriate, using BL3 practices and containment 
equipment.
    Exotic plant pathogens and animal pathogens of domestic livestock 
and poultry are restricted and may require special laboratory design, 
operation and containment features not addressed in Biosafety in 
Microbiological and Biomedical Laboratories (see Section V-C, Footnotes 
and References of Sections I through IV). For information regarding the 
importation, possession, or use of these agents see Sections V-G and V-
H, Footnotes and References of Sections I through IV.
    Risk mitigation strategies employed in contained settings are not 
likely to differ for GDMOs compared to other gene modified organisms in 
the laboratory. However, given the relative newness of GDMO technology 
and its use in biomedical research, any risk assessment is likely to 
have greater uncertainty regarding potential risks. Section II-A-3 is 
proposed to be amended to provide additional guidance for conducting 
these assessments by insertion of new paragraphs five and six:
    Section II-A-3 is proposed to be amended to:
    In deciding on the appropriate containment for an experiment, the 
first step is to assess the risk of the agent itself. Appendix B, 
Classification of Human Etiologic Agents on the Basis of Hazard, 
classifies agents into Risk Groups based on an assessment of their 
ability to cause disease in humans and the available treatments for 
such disease. Once the Risk Group of the agent is identified, this 
should be followed by a thorough consideration of how the agent is to 
be manipulated. Factors to be considered in determining the level of 
containment include agent factors such as: virulence, pathogenicity, 
infectious dose, environmental stability, route of spread, 
communicability, operations, quantity, availability of vaccine or 
treatment, and gene product effects such as toxicity, physiological 
activity, and allergenicity. Any strain that is known to be more 
hazardous than the parent (wild-type) strain should be considered for 
handling at a higher containment level. Certain attenuated strains or 
strains that have been demonstrated to have irreversibly lost known 
virulence factors may qualify for a reduction of the containment level 
compared to the Risk Group assigned to the parent strain (see Section 
V-B, Footnotes and References of Sections I-IV).
    While the starting point for the risk assessment is based on the 
identification of the Risk Group of the parent agent, as technology 
moves forward, it may be possible to develop an organism containing 
genetic sequences from multiple sources such that the parent agent may 
not be obvious. In such cases, the risk assessment should include at 
least two levels of analysis. The first involves a consideration of the 
Risk Groups of the source(s) of the sequences and the second involves 
an assessment of the functions that may be encoded by these sequences 
(e.g., virulence or transmissibility). It may be prudent to first 
consider the highest Risk Group classification of all agents that are 
the source of sequences included in the construct. Other factors to be 
considered include the percentage of the genome contributed by each 
parent agent and the predicted function or intended purpose of each 
contributing sequence. The initial assumption should be that all 
sequences will function as they did in the original host context.
    The Principal Investigator and Institutional Biosafety Committee 
must also be cognizant that the combination of certain sequences in a 
new biological context may result in an organism whose risk profile 
could be higher than that of the contributing organisms or sequences. 
The synergistic function of these sequences may be one of the key

[[Page 54335]]

attributes to consider in deciding whether a higher containment level 
is warranted, at least until further assessments can be carried out. A 
new biosafety risk may occur with an organism formed through 
combination of sequences from a number of organisms or due to the 
synergistic effect of combining transgenes that results in a new 
phenotype.
    A final assessment of risk based on these considerations is then 
used to set the appropriate containment conditions for the experiment 
(see Section II-B, Containment). The appropriate containment level may 
be equivalent to the Risk Group classification of the agent or it may 
be raised or lowered as a result of the above considerations. The 
Institutional Biosafety Committee must approve the risk assessment and 
the biosafety containment level for recombinant or synthetic nucleic 
acid experiments described in Sections III-A, Experiments that Require 
NIH Director Approval and Institutional Biosafety Committee Approval, 
Before Initiation; III-B, Experiments that Require NIH OSP and 
Institutional Biosafety Committee Approval Before Initiation; III-C, 
Experiments Involving Human Gene Transfer that Require Institutional 
Biosafety Committee Approval Prior to Initiation; III-D, Experiments 
that Require Institutional Biosafety Committee Approval Before 
Initiation.
    Research involving gene drive modified organisms may require risk 
assessments that incorporate a broader scope of considerations because 
of greater uncertainty of the technology and potential uncertainty of 
the impact of the newly modified organism. Specific attention must be 
paid to risks of an unintended release from the laboratory and the 
potential impact on humans, other populations of organisms, and the 
environment.
    Considerations for conducting risk assessments for research 
involving gene drive modified organisms might include:
    1. The specific types of manipulations based on:
    a. Function or intended function of the genetic/gene drive 
construct (i.e., a designed or engineered assembly of sequences);
    b. Source of the genetic material (e.g., sequences of transgenes) 
in the construct;
    c. The modifications to the construct;
    d. Whether it is possible to predict the consequences of a 
construct, including the recognition of an unintended gene drive (i.e., 
construct not specifically designed as a gene drive but nonetheless 
having properties of a gene drive) and the possible consequences of 
escape into the environment;
    e. The potential ability of the gene drive to spread or persist in 
local populations;
    2. Options for approaches to risk mitigation for specific types of 
risks in experiments or when dealing with a high degree of uncertainty 
about risks;
    3. Considerations for implementing more stringent containment 
measures until biosafety data are accrued to support lowering 
containment.
    Careful consideration should be given to the types of manipulation 
planned for some higher Risk Group agents. For example, the RG2 dengue 
viruses may be cultured under the Biosafety Level (BL) 2 containment 
(see Section II-B); however, when such agents are used for animal 
inoculation or transmission studies, a higher containment level is 
recommended. Similarly, RG3 agents such as Venezuelan equine 
encephalomyelitis and yellow fever viruses should be handled at a 
higher containment level for animal inoculation and transmission 
experiments.
    Individuals working with human immunodeficiency virus (HIV), 
hepatitis B virus (HBV) or other bloodborne pathogens should consult 
the applicable Occupational Safety and Health Administration (OSHA) 
regulation, 29 CFR 1910.1030, and OSHA publication 3127 (1996 revised). 
BL2 containment is recommended for activities involving all blood-
contaminated clinical specimens, body fluids, and tissues from all 
humans, or from HIV- or HBV-infected or inoculated laboratory animals. 
Activities such as the production of research-laboratory scale 
quantities of HIV or other bloodborne pathogens, manipulating 
concentrated virus preparations, or conducting procedures that may 
produce droplets or aerosols, are performed in a BL2 facility using the 
additional practices and containment equipment recommended for BL3. 
Activities involving industrial scale volumes or preparations of 
concentrated HIV are conducted in a BL3 facility, or BL3 Large Scale if 
appropriate, using BL3 practices and containment equipment.
    Exotic plant pathogens and animal pathogens of domestic livestock 
and poultry are restricted and may require special laboratory design, 
operation and containment features not addressed in Biosafety in 
Microbiological and Biomedical Laboratories (see Section V-C, Footnotes 
and References of Sections I through IV). For information regarding the 
importation, possession, or use of these agents see Sections V-G and V-
H, Footnotes and References of Sections I through IV.
    In 2012 when the NIH Guidelines were updated to expand the scope to 
cover synthetic nucleic acid molecules, Section III-C and Section III-
F-1 were amended to exempt research with certain oligonucleotides based 
on the lower risk posed by their transient nature. These sections also 
outlined criteria for higher risk nucleic acids that would not be 
exempt (e.g., nucleic acids that replicated, were transcribed, 
translated, or integrated etc.). At that time, much research with 
oligonucleotides was likely to involve a delivery method using a 
recombinant nucleic acid molecule (e.g., viral vector or plasmid), and 
thus would still be subject to the NIH Guidelines. Since then, gene 
editing using CRISPR/Cas systems and non-recombinant delivery methods 
(e.g., lipid nanoparticles) has come into more common use. Currently, 
transgenic organisms with the same genetic modification may or may not 
be subject to the NIH Guidelines depending on the method of generation 
(e.g., recombinant viral vector delivery and expression of Cas9 and 
guide RNAs vs. lipid nanoparticle delivery of protein Cas9 and guide 
RNAs). Because of the higher risks associated with stable genetic 
modifications to viruses, cells, or organisms, Sections III-C and III-
F-1 each have a criterion that precludes the exemption of nucleic acids 
that integrate, the main method to introduce such changes in 2012. To 
avoid exempting certain gene editing approaches or GDMOs, the language 
in Sections III-C and III-F-1 is proposed to be amended to replace the 
criterion involving integration with a broader criterion covering the 
introduction of a stable genetic modification.
    Section III-C-1 currently states in part:

Section III-C-1. Experiments Involving the Deliberate Transfer of 
Recombinant or Synthetic Nucleic Acid Molecules, or DNA or RNA Derived 
From Recombinant or Synthetic Nucleic Acid Molecules, Into One or More 
Human Research Participants

    Human gene transfer is the deliberate transfer into human research 
participants of either:
    1. Recombinant nucleic acid molecules, or DNA or RNA derived from 
recombinant nucleic acid molecules, or
    2. Synthetic nucleic acid molecules, or DNA or RNA derived from 
synthetic nucleic acid molecules, that meet any one of the following 
criteria:
    a. Contain more than 100 nucleotides; or

[[Page 54336]]

    b. Possess biological properties that enable integration into the 
genome (e.g., cis elements involved in integration); or
    c. Have the potential to replicate in a cell; or
    d. Can be translated or transcribed.
    This portion of Section III-C-1 1 is proposed to be amended to:

Section III-C-1. Experiments Involving the Deliberate Transfer of 
Recombinant or Synthetic Nucleic Acid Molecules, or DNA or RNA Derived 
From Recombinant or Synthetic Nucleic Acid Molecules, Into One or More 
Human Research Participants

    Human gene transfer is the deliberate transfer into human research 
participants of either:
    1. Recombinant nucleic acid molecules, or DNA or RNA derived from 
recombinant nucleic acid molecules, or
    2. Synthetic nucleic acid molecules, or DNA or RNA derived from 
synthetic nucleic acid molecules, that meet any one of the following 
criteria:
    a. Contain more than 100 nucleotides; or
    b. Possess biological properties that enable introduction of stable 
genetic modifications into the genome (e.g., cis elements involved in 
integration, gene editing); or
    c. Have the potential to replicate in a cell; or
    d. Can be translated or transcribed.
    Section III-F-1 currently states:
    Section III-F-1. Those synthetic nucleic acids that: (1) can 
neither replicate nor generate nucleic acids that can replicate in any 
living cell (e.g., oligonucleotides or other synthetic nucleic acids 
that do not contain an origin of replication or contain elements known 
to interact with either DNA or RNA polymerase), and (2) are not 
designed to integrate into DNA, and (3) do not produce a toxin that is 
lethal for vertebrates at an LD50 of less than 100 nanograms per 
kilogram body weight. If a synthetic nucleic acid is deliberately 
transferred into one or more human research participants and meets the 
criteria of Section III-C, it is not exempt under this Section.
    Section III-F-1 is proposed to be amended to:
    Section III-F-1. Those synthetic nucleic acids that: (1) can 
neither replicate nor generate nucleic acids that can replicate in any 
living cell (e.g., oligonucleotides or other synthetic nucleic acids 
that do not contain an origin of replication or contain elements known 
to interact with either DNA or RNA polymerase), and (2) are not 
designed to introduce a stable genetic modification, and (3) do not 
produce a toxin that is lethal for vertebrates at an LD50 of less than 
100 nanograms per kilogram body weight. If a synthetic nucleic acid is 
deliberately transferred into one or more human research participants 
and meets the criteria of Section III-C, it is not exempt under this 
Section.
    To provide guidance on physical containment for research involving 
GDMOs, Section III-D is proposed to be amended in multiple subsections 
to require that experiments involving GDMOs be conducted at a minimum 
of BL2 containment to provide the appropriate laboratory practices, 
containment equipment, and special laboratory design to protect 
laboratory workers, the public, and local ecosystems. A section 
specific to experiments involving GDMOs is proposed to be added as 
Section III-D-8. Sections III-D-4, III-D-5, and III-E-3, which cover 
experiments with whole animals, plants, and transgenic rodents, are 
also proposed to be amended to reference Section III-D-8.
    Section III-D-4, which is part of Section III-D, Experiments that 
Require Institutional Biosafety Committee Approval Before Initiation, 
currently states:

Section III-D-4. Experiments Involving Whole Animals

    This section covers experiments involving whole animals in which 
the animal's genome has been altered by stable introduction of 
recombinant or synthetic nucleic acid molecules, or nucleic acids 
derived therefrom, into the germ-line (transgenic animals) and 
experiments involving viable recombinant or synthetic nucleic acid 
molecule-modified microorganisms tested on whole animals. For the 
latter, other than viruses which are only vertically transmitted, the 
experiments may not be conducted at BL1-N containment. A minimum 
containment of BL2 or BL2-N is required.
    Caution--Special care should be used in the evaluation of 
containment conditions for some experiments with transgenic animals. 
For example, such experiments might lead to the creation of novel 
mechanisms or increased transmission of a recombinant pathogen or 
production of undesirable traits in the host animal. In such cases, 
serious consideration should be given to increasing the containment 
conditions.
    Section III-D-4-a. Recombinant or synthetic nucleic acid molecules, 
or DNA or RNA molecules derived therefrom, from any source except for 
greater than two-thirds of eukaryotic viral genome may be transferred 
to any non-human vertebrate or any invertebrate organism and propagated 
under conditions of physical containment comparable to BL1 or BL1-N and 
appropriate to the organism under study (see Section V-B, Footnotes and 
References of Sections I-IV). Animals that contain sequences from viral 
vectors, which do not lead to transmissible infection either directly 
or indirectly as a result of complementation or recombination in 
animals, may be propagated under conditions of physical containment 
comparable to BL1 or BL1-N and appropriate to the organism under study. 
Experiments involving the introduction of other sequences from 
eukaryotic viral genomes into animals are covered under Section III-D-
4-b, Experiments Involving Whole Animals. For experiments involving 
recombinant or synthetic nucleic acid molecule-modified Risk Groups 2, 
3, 4, or restricted organisms, see Sections V-A, V-G, and V-L, 
Footnotes and References of Sections I-IV. It is important that the 
investigator demonstrate that the fraction of the viral genome being 
utilized does not lead to productive infection. A U.S. Department of 
Agriculture permit is required for work with plant or animal pathogens 
(see Section V-G, Footnotes and References of Sections I-IV).
    Section III-D-4-b. For experiments involving recombinant or 
synthetic nucleic acid molecules, or DNA or RNA derived therefrom, 
involving whole animals, including transgenic animals, and not covered 
by Section III-D-1, Experiments Using Human or Animal Pathogens (Risk 
Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-
Vector Systems), or Section III-D-4-a, the appropriate containment 
shall be determined by the Institutional Biosafety Committee.
    Section III-D-4-c. Exceptions under Section III-D-4, Experiments 
Involving Whole Animals
    Section III-D-4-c-(1). Experiments involving the generation of 
transgenic rodents that require BL1 containment are described under 
Section III-E-3, Experiments Involving Transgenic Rodents.
    Section III-D-4-c-(2). The purchase or transfer of transgenic 
rodents is exempt from the NIH Guidelines under Section III-F, Exempt 
Experiments (see Appendix C-VII, The Purchase or Transfer of Transgenic 
Rodents).
    Section III-D-4 is proposed to be amended to state:

Section III-D-4. Experiments Involving Whole Animals

    This section covers experiments involving deliberate transfer of 
recombinant or synthetic nucleic acid

[[Page 54337]]

molecules, DNA or RNA derived from recombinant or synthetic nucleic 
acid molecules, or recombinant or synthetic nucleic acid molecule-
modified microorganisms into whole animals and experiments involving 
whole animals in which the animal's genome has been altered by 
recombinant or synthetic nucleic acid molecules, or nucleic acids 
derived therefrom, into the germ-line (transgenic animals). Experiments 
involving gene drive modified animals or experiments involving viable 
recombinant or synthetic nucleic acid molecule-modified microorganisms, 
except for viruses that are only vertically transmitted, may not be 
conducted at BL1-N containment. A minimum containment of BL2 or BL2-N 
is required (see Section III-D-8).
    Caution--Special care should be used in the evaluation of 
containment conditions for some experiments with transgenic animals. 
For example, such experiments might lead to the creation of novel 
mechanisms (e.g., a gene drive; refer to Section III-D-8) or increased 
transmission of a recombinant pathogen or production of undesirable 
traits in the host animal. In such cases, serious consideration should 
be given to increasing the containment conditions.
    Section III-D-4-a. Recombinant or synthetic nucleic acid molecules, 
or DNA or RNA molecules derived therefrom, from any source except for 
greater than two-thirds of eukaryotic viral genome may be transferred 
to any non-human vertebrate or any invertebrate organism and propagated 
under conditions of physical containment comparable to BL1 or BL1-N and 
appropriate to the organism under study (see Section V-B, Footnotes and 
References of Sections I-IV). Animals that contain sequences from viral 
vectors, which do not lead to transmissible infection either directly 
or indirectly as a result of complementation or recombination in 
animals, may be propagated under conditions of physical containment 
comparable to BL1 or BL1-N and appropriate to the organism under study. 
Experiments involving the introduction of other sequences from 
eukaryotic viral genomes into animals are covered under Section III-D-
4-b, Experiments Involving Whole Animals. For experiments involving 
recombinant or synthetic nucleic acid molecule-modified Risk Groups 2, 
3, 4, or restricted organisms, see Sections V-A, V-G, and V-L, 
Footnotes and References of Sections I-IV. It is important that the 
investigator demonstrate that the fraction of the viral genome being 
utilized does not lead to productive infection. A U.S. Department of 
Agriculture permit is required for work with plant or animal pathogens 
(see Section V-G, Footnotes and References of Sections I-IV).
    Section III-D-4-b. For experiments involving recombinant or 
synthetic nucleic acid molecules, or DNA or RNA derived therefrom, 
involving whole animals, including transgenic animals, and not covered 
by Section III-D-1, Experiments Using Human or Animal Pathogens (Risk 
Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-
Vector Systems), or Section III-D-4-a, the appropriate containment 
shall be determined by the Institutional Biosafety Committee. 
Experiments involving gene drive modified animals generated by 
recombinant or synthetic nucleic acid molecules shall be conducted at a 
minimum of BL2 or BL2-N (see Section III-D-8).
    Section III-D-4-c. Exceptions under Section III-D-4, Experiments 
Involving Whole Animals
    Section III-D-4-c-(1). Experiments involving the generation of 
transgenic rodents that require BL1 containment are described under 
Section III-E-3, Experiments Involving Transgenic Rodents.
    Section III-D-4-c-(2). The purchase or transfer of BL1 transgenic 
rodents is exempt from the NIH Guidelines under Section III-F, Exempt 
Experiments (see Appendix C-VII, The Purchase or Transfer of Transgenic 
Rodents).
    Section III-D-4-c-(3). Experiments involving the generation or use 
of gene drive modified animals require a minimum of BL2 containment and 
are covered under III-D-8, Experiments Involving Gene Drive Modified 
Organisms.
    Section III-D-5 currently states in part:

Section III-D-5. Experiments Involving Whole Plants

    Experiments to genetically engineer plants by recombinant or 
synthetic nucleic acid molecule methods, to use such plants for other 
experimental purposes (e.g., response to stress), to propagate such 
plants, or to use plants together with microorganisms or insects 
containing recombinant or synthetic nucleic acid molecules, may be 
conducted under the containment conditions described in Sections III-D-
5-a through III-D-5-e. If experiments involving whole plants are not 
described in Section III-D-5 and do not fall under Sections III-A, III-
B, III-D or III-F, they are included in Section III-E.
    This portion of Section III-D-5 is proposed to be amended to:

Section III-D-5. Experiments Involving Whole Plants

    Experiments to genetically engineer plants by recombinant or 
synthetic nucleic acid molecule methods, to use such plants for other 
experimental purposes (e.g., response to stress), to propagate such 
plants, or to use plants together with microorganisms or insects 
containing recombinant or synthetic nucleic acid molecules, may be 
conducted under the containment conditions described in Sections III-D-
5-a through III-D-5-e. If experiments involving whole plants are not 
described in Section III-D-5 and do not fall under Sections III-A, III-
B, III-D or III-F, they are included in Section III-E. Experiments 
involving the generation or use of gene drive modified organisms 
require a minimum of BL2 containment and are described under Section 
III-D-8, Experiments Involving Gene Drive Modified Organisms.
    Section III-D-8 is proposed to be added to state:

Section III-D-8. Experiments Involving Gene Drive Modified Organisms

    Experiments involving gene drive modified organisms generated by 
recombinant or synthetic nucleic acid molecules shall be conducted at a 
minimum of Biosafety Level (BL) 2, BL2-N (Animals) or BL2-P (plant) 
containment.
    Only transgenic rodents that may be contained under BL1 are covered 
under Section III-E-3. Section III-E-3 is proposed to be amended to 
reference the new Section III-D-8 to reinforce that research with GDMOs 
shall be conducted at a minimum of BL2. Section III-E-3, which is part 
of Section III-E, Experiments that Require Institutional Biosafety 
Committee Notice Simultaneous with Initiation, states in part:

Section III-E-3. Experiments Involving Transgenic Rodents

    This section covers experiments involving the generation of rodents 
in which the animal's genome has been altered by stable introduction of 
recombinant or synthetic nucleic acid molecules, or nucleic acids 
derived therefrom, into the germ-line (transgenic rodents). Only 
experiments that require BL1 containment are covered under this 
section; experiments that require BL2, BL3, or BL4 containment are 
covered under Section III-D-4, Experiments Involving Whole Animals.

[[Page 54338]]

    This portion of Section III-E-3 is proposed to be amended to:

Section III-E-3. Experiments Involving Transgenic Rodents

    This section covers experiments involving the generation or use of 
rodents in which the animal's genome has been altered by stable 
introduction of recombinant or synthetic nucleic acid molecules, or 
nucleic acids derived therefrom, into the germ-line (transgenic 
rodents). Only experiments that require BL1 containment are covered 
under this section; experiments that require BL2, BL3, or BL4 
containment are covered under Section III-D-4, Experiments Involving 
Whole Animals or Section III-D-8, Experiments Involving Gene Drive 
Modified Organisms.
    In the NExTRAC report, the committee recommended that NIH should 
require appropriate expertise in the review of gene drive research by 
IBC members and BSO. Portions of Section IV-B are proposed to be 
amended regarding institutional responsibilities for the establishment 
of IBCs and requirements for BSOs.
    Section IV-B-1-c currently states:
    Section IV-B-1-c. Appoint a Biological Safety Officer (who is also 
a member of the Institutional Biosafety Committee) if the institution: 
(i) conducts recombinant or synthetic nucleic acid molecule research at 
Biosafety Level (BL) 3 or BL4, or (ii) engages in large-scale (greater 
than 10 liters) research. The Biological Safety Officer carries out the 
duties specified in Section IV-B-3.
    Section IV-B-1-c is proposed to be amended to:
    Section IV-B-1-c. Appoint a Biological Safety Officer (who is also 
a member of the Institutional Biosafety Committee) if the institution: 
(i) conducts recombinant or synthetic nucleic acid molecule research at 
Biosafety Level (BL) 3 or BL4, (ii) engages in large-scale (greater 
than 10 liters) research or (iii) conducts research involving gene 
drive modified organisms. The Biological Safety Officer carries out the 
duties specified in Section IV-B-3.
    Section IV-B-2-a, Membership and Procedures of IBCs currently 
states in part:
    Section IV-B-2-a-(1). The Institutional Biosafety Committee must 
comprise no fewer than five members so selected that they collectively 
have experience and expertise in recombinant or synthetic nucleic acid 
molecule technology and the capability to assess the safety of 
recombinant or synthetic nucleic acid molecule research and to identify 
any potential risk to public health or the environment. At least two 
members shall not be affiliated with the institution (apart from their 
membership on the Institutional Biosafety Committee) and who represent 
the interest of the surrounding community with respect to health and 
protection of the environment (e.g., officials of state or local public 
health or environmental protection agencies, members of other local 
governmental bodies, or persons active in medical, occupational health, 
or environmental concerns in the community). The Institutional 
Biosafety Committee shall include at least one individual with 
expertise in plant, plant pathogen, or plant pest containment 
principles when experiments utilizing Appendix L, Physical and 
Biological Containment for Recombinant or Synthetic Nucleic Acid 
Molecule Research Involving Plants, require prior approval by the 
Institutional Biosafety Committee. The Institutional Biosafety 
Committee shall include at least one scientist with expertise in animal 
containment principles when experiments utilizing Appendix M, Physical 
and Biological Containment for Recombinant or Synthetic Nucleic Acid 
Molecule Research Involving Animals, require Institutional Biosafety 
Committee prior approval. When the institution conducts recombinant or 
synthetic nucleic acid molecule research at BL3, BL4, or Large Scale 
(greater than 10 liters), a Biological Safety Officer is mandatory and 
shall be a member of the Institutional Biosafety Committee (see Section 
IV-B-3, Biological Safety Officer). When the institution participates 
in or sponsors recombinant or synthetic nucleic acid molecule research 
involving human research participants, the institution must ensure that 
the Institutional Biosafety Committee has adequate expertise and 
training (using ad hoc consultants as deemed necessary). Institutional 
Biosafety Committee approval must be obtained from the clinical trial 
site.
    Section IV-B-2-a-(1) is proposed to be amended to read:
    Section IV-B-2-a-(1). The Institutional Biosafety Committee must 
comprise no fewer than five members so selected that they collectively 
have experience and expertise in recombinant or synthetic nucleic acid 
molecule technology and the capability to assess the safety of 
recombinant or synthetic nucleic acid molecule research and to identify 
any potential risk to public health or the environment. At least two 
members shall not be affiliated with the institution (apart from their 
membership on the Institutional Biosafety Committee) and who represent 
the interest of the surrounding community with respect to health and 
protection of the environment (e.g., officials of state or local public 
health or environmental protection agencies, members of other local 
governmental bodies, or persons active in medical, occupational health, 
or environmental concerns in the community). The Institutional 
Biosafety Committee shall include at least one individual with 
expertise in plant, plant pathogen, or plant pest containment 
principles when experiments utilizing Appendix L, Physical and 
Biological Containment for Recombinant or Synthetic Nucleic Acid 
Molecule Research Involving Plants, require prior approval by the 
Institutional Biosafety Committee. The Institutional Biosafety 
Committee shall include at least one scientist with expertise in animal 
containment principles when experiments utilizing Appendix M, Physical 
and Biological Containment for Recombinant or Synthetic Nucleic Acid 
Molecule Research Involving Animals, require Institutional Biosafety 
Committee prior approval. When the institution conducts research 
involving gene drive modified organisms the institution must ensure 
that the Institutional Biosafety Committee has adequate expertise 
(e.g., specific species containment, ecological or environmental risk 
assessment) using ad hoc consultants if necessary. When the institution 
conducts recombinant or synthetic nucleic acid molecule research at 
BL3, BL4, or Large Scale (greater than 10 liters) or research involving 
gene drive modified organisms, a Biological Safety Officer is mandatory 
and shall be a member of the Institutional Biosafety Committee (see 
Section IV-B-3, Biological Safety Officer). When the institution 
conducts research with gene drive modified organisms, the impact on 
ecosystems should be assessed by the Institutional Biosafety Committee 
(see Section V-N, Footnotes and References of Sections I-IV). When the 
institution participates in or sponsors recombinant or synthetic 
nucleic acid molecule research involving human research participants, 
the institution must ensure that the Institutional Biosafety Committee 
has adequate expertise and training (using ad hoc consultants if 
necessary). Institutional Biosafety Committee approval must be obtained 
from the clinical trial site.
    Section IV-B-3, Biological Safety Officer (BSO), states in part:
    Section IV-B-3-a. The institution shall appoint a Biological Safety 
Officer if it engages in large-scale research or

[[Page 54339]]

production activities involving viable organisms containing recombinant 
or synthetic nucleic acid molecules.
    Section IV-B-3-a is proposed to be amended to clarify the 
requirement for a BSO to be a member of the IBC. A new Section IV-B-3-c 
is proposed to be added to require a BSO for research involving GDMOs. 
The current IV-B-3-c sections will be re-lettered to IV-B-3-d.
    Section IV-B-3-a. The institution shall appoint a Biological Safety 
Officer if it engages in large-scale research or production activities 
involving viable organisms containing recombinant or synthetic nucleic 
acid molecules. The Biological Safety Officer shall be a member of the 
Institutional Biosafety Committee.
    Section IV-B-3-c. The institution shall appoint a Biological Safety 
Officer if it engages in recombinant or synthetic nucleic acid molecule 
research that involves gene drive modified organisms. The Biological 
Safety Officer shall be a member of the Institutional Biosafety 
Committee.
    To emphasize that GDMOs may have an impact on ecosystems, a new 
footnote and reference for Sections I through IV is proposed to be 
added.
    Section V-N is proposed to state:
    Section V-N Determination of whether a gene drive modified organism 
has a potential for serious detrimental impact on managed 
(agricultural, forest, grassland) or natural ecosystems should be made 
by the Principal Investigator and the Institutional Biosafety 
Committee, in consultation with scientists knowledgeable of gene drive 
technology, the environment, and ecosystems in the geographic area of 
the research.
    Since research with GDMOs shall be conducted at a minimum of 
Biosafety Level 2, research involving host vector system organisms 
modified by a gene drive will not be exempt. Therefore, the exceptions 
(Appendices C-III-A and C-IV-A) to Appendices C-III and C-IV, 
Saccharomyces and Kluyveromyces Host-Vector Systems, respectively, are 
proposed to be amended.
    Appendices C-III-A Exceptions and C-IV-A Exceptions currently 
state:
    The following categories are not exempt from the NIH Guidelines: 
(i) experiments described in Section III-B which require NIH OSP and 
Institutional Biosafety Committee approval before initiation, (ii) 
experiments involving DNA from Risk Groups 3, 4, or restricted 
organisms (see Appendix B, Classification of Human Etiologic Agents on 
the Basis of Hazard, and Sections V-G and V-L, Footnotes and References 
of Sections I through IV) or cells known to be infected with these 
agents may be conducted under containment conditions specified in 
Section III-D-2 with prior Institutional Biosafety Committee review and 
approval, (iii) large-scale experiments (e.g., more than 10 liters of 
culture), and (iv) experiments involving the deliberate cloning of 
genes coding for the biosynthesis of molecules toxic for vertebrates 
(see Appendix F, Containment Conditions for Cloning of Genes Coding for 
the Biosynthesis of Molecules Toxic for Vertebrates).
    Appendices C-III-A Exceptions and C-IV-A Exceptions are proposed to 
be amended to state:
    The following categories are not exempt from the NIH Guidelines: 
(i) experiments described in Section III-B, which require NIH OSP and 
Institutional Biosafety Committee approval before initiation; (ii) 
experiments involving DNA from Risk Groups 3, 4, or restricted 
organisms (see Appendix B, Classification of Human Etiologic Agents on 
the Basis of Hazard, and Sections V-G and V-L, Footnotes and References 
of Sections I through IV) or cells known to be infected with these 
agents may be conducted under containment conditions specified in 
Section III-D-2 with prior Institutional Biosafety Committee review and 
approval; (iii) large-scale experiments (e.g., more than 10 liters of 
culture), (iv) experiments involving the deliberate cloning of genes 
coding for the biosynthesis of molecules toxic for vertebrates (see 
Appendix F, Containment Conditions for Cloning of Genes Coding for the 
Biosynthesis of Molecules Toxic for Vertebrates), and (v) experiments 
involving gene drive modified organisms (Section III-D-8). To provide 
additional guidance on containment for work with arthropods, Appendices 
G, L, and M are proposed to reference the Arthropod Containment 
Guidelines, which specifically outline practices and procedures for 
arthropod research, and the addendum Arthropod Containment Guidelines, 
which articulates containment practices for gene drive modified 
arthropods. Appendix G-III and Footnotes and References of Appendix G 
will also be modified to reference the current edition of the reference 
source BMBL and to correct an erroneous second citation of the BMBL.
    Appendix G-III-A currently states:
    Appendix G-III-A. Biosafety in Microbiological and Biomedical 
Laboratories, 5th edition, U.S. Department of Health and Human 
Services, Public Health Service, Centers for Disease Control and 
Prevention, Atlanta, Georgia, and National Institutes of Health, 
Bethesda, Maryland.
    Appendix G-III-A is proposed to be amended to state:
    Appendix G-III-A. Biosafety in Microbiological and Biomedical 
Laboratories, 6th edition, U.S. Department of Health and Human 
Services, Public Health Service, Centers for Disease Control and 
Prevention, Atlanta, Georgia, and National Institutes of Health, 
Bethesda, Maryland.
    Appendix G-III-B currently states:
    Appendix G-III-B. Biosafety in Microbiological and Biomedical 
Laboratories, 3rd edition, May 1993, U.S. DHHS, Public Health Service, 
Centers for Disease Control and Prevention, Atlanta, Georgia, and NIH, 
Bethesda, Maryland.
    Appendix G-III-B is proposed to be amended to state:
    Appendix G-III-B. Arthropod Containment Guidelines, Version 3.2, 
2019, and Addendum 1 Containment Practices for Arthropods Modified with 
Engineered Transgenes Capable of Gene Drive, 2022, American Committee 
of Medical Entomology, American Society of Tropical Medicine and 
Hygiene, Arlington, Virginia. Appendices L and M specify containment 
conditions and practices for plants and animals, respectively, that 
preclude the use of containment as specified in Appendix G. Both 
Appendices L and M will be modified to incorporate the Arthropod 
Containment Guidelines and cross-reference to Appendix G-III-B.
    Appendix L-III-C currently states:

Appendix L-III-C. Biological Containment Practices (Macroorganisms)

    Appendix L-III-C-1. Effective dissemination of arthropods and other 
small animals can be prevented by using one or more of the following 
procedures: (i) use non-flying, flight-impaired, or sterile arthropods; 
(ii) use non-motile or sterile strains of small animals; (iii) conduct 
experiments at a time of year that precludes the survival of escaping 
organisms; (iv) use animals that have an obligate association with a 
plant that is not present within the dispersal range of the organism; 
or (v) prevent the escape of organisms present in run-off water by 
chemical treatment or evaporation of run-off water.
    Appendix L-III-C is proposed to be amended to:

Appendix L-III-C. Biological Containment Practices (Macroorganisms)

    Appendix L-III-C-1. Effective dissemination of arthropods and other 
small animals can be prevented by using

[[Page 54340]]

one or more of the following procedures: (i) use non-flying, flight-
impaired, or sterile arthropods; (ii) use non-motile or sterile strains 
of small animals; (iii) conduct experiments at a time of year that 
precludes the survival of escaping organisms; (iv) use animals that 
have an obligate association with a plant that is not present within 
the dispersal range of the organism; or (v) prevent the escape of 
organisms present in run-off water by chemical treatment or evaporation 
of run-off water. Containment for arthropods is described in the 
Arthropod Containment Guidelines and Addendum 1 Containment Practices 
for Arthropods Modified with Engineered Transgenes Capable of Gene 
Drive (see Appendix G-III-B).
    Appendix M-III-D currently states:
    Appendix M-III-D. Other research with non-laboratory animals, which 
may not appropriately be conducted under conditions described in 
Appendix M, may be conducted safely by applying practices routinely 
used for controlled culture of these biota. In aquatic systems, for 
example, BL1 equivalent conditions could be met by utilizing growth 
tanks that provide adequate physical means to avoid the escape of the 
aquatic species, its gametes, and introduced exogenous genetic 
material. A mechanism shall be provided to ensure that neither the 
organisms nor their gametes can escape into the supply or discharge 
system of the rearing container (e.g., tank, aquarium, etc.) Acceptable 
barriers include appropriate filtration, irradiation, heat treatment, 
chemical treatment, etc. Moreover, the top of the rearing container 
shall be covered to avoid escape of the organism and its gametes. In 
the event of tank rupture, leakage, or overflow, the construction of 
the room containing these tanks should prevent the organisms and 
gametes from entering the building's drains before the organism and its 
gametes have been inactivated.
    Other types of non-laboratory animals (e.g., nematodes, arthropods, 
and certain forms of smaller animals) may be accommodated by using the 
appropriate BL1 through BL4 or BL1-P through BL4-P containment 
practices and procedures as specified in Appendices G and L.
    Appendix M-III-D is proposed to be amended to:
    Appendix M-III-D. Research with animals, which may not 
appropriately be conducted under conditions described in Appendix M, 
may be conducted safely by applying practices routinely used for 
controlled culture of these biota. In aquatic systems, for example, BL1 
equivalent conditions could be met by utilizing growth tanks that 
provide adequate physical means to avoid the escape of the aquatic 
species, its gametes, and introduced exogenous genetic material. A 
mechanism shall be provided to ensure that neither the organisms nor 
their gametes can escape into the supply or discharge system of the 
rearing container (e.g., tank, aquarium, etc.) Acceptable barriers 
include appropriate filtration, irradiation, heat treatment, chemical 
treatment, etc. Moreover, the top of the rearing container shall be 
covered to avoid escape of the organism and its gametes. In the event 
of tank rupture, leakage, or overflow, the construction of the room 
containing these tanks should prevent the organisms and gametes from 
entering the building's drains before the organism and its gametes have 
been inactivated.
    Other types of animals (e.g., nematodes, arthropods, and certain 
forms of smaller animals) may be accommodated by using the appropriate 
BL1 through BL4 or BL1-P through BL4-P containment practices and 
procedures as specified in Appendices G and L. Containment for 
arthropods is described in the Arthropod Containment Guidelines and 
Addendum 1 Containment Practices for Arthropods Modified with 
Engineered Transgenes Capable of Gene Drive (see Appendix G-III-B).
    The term ``helper virus'' is used in multiple sections of the NIH 
Guidelines to refer to the missing functions provided to a defective 
virus. However, helper systems (e.g., transient transfection systems, 
packaging cell lines, replicon systems, etc.) are more commonly used 
than a helper virus. NIH OSP has interpreted the term ``helper virus'' 
to extend to the use of helper systems because they are also associated 
with the risk of generation of replication competent virus. To clarify 
the language in the NIH Guidelines, the term ``helper virus'' will be 
replaced in Sections III-D-3, and III-E-1 with the term ``helper 
systems''.
    The risk group classification in Appendix B of two viruses, West 
Nile virus and St. Louis encephalitis virus, are proposed to be changed 
from RG3 to RG2 to be consistent with the risk assessment that is 
articulated in the current edition of the BMBL.
    Appendix B-III-D currently states in part:
    Appendix B-III-D. Risk Group 3 (RG3)--Viruses and Prions.
    Alphaviruses (Togaviruses)--Group A Arboviruses currently states in 
part:
    --St. Louis encephalitis virus.
    Flaviviruses--Group B Arboviruses currently states in part:
    --West Nile virus (WNV).
    Appendix B-II-D is proposed to be amended to state:
    Appendix B-II-D. Risk Group 2 (RG2)--Viruses.
    Alphaviruses (Togaviruses)--Group A Arboviruses.
    --St. Louis encephalitis virus.
    Flaviviruses--Group B Arboviruses.
    --West Nile virus (WNV).

    Dated: August 3, 2023.
Tara A. Schwetz,
Acting Principal Deputy Director, National Institutes of Health.
[FR Doc. 2023-17178 Filed 8-9-23; 8:45 am]
BILLING CODE 4140-01-P