[Federal Register Volume 60, Number 98 (Monday, May 22, 1995)]
[Notices]
[Pages 27206-27216]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-12405]
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Recombinant DNA Research: Proposed Actions Under the Guidelines
Agency: National Institutes of Health (NIH), PHS, DHHS.
Action: Notice of Proposed Actions Under the NIH Guidelines for
Research Involving Recombinant DNA Molecules (59 FR 34496).
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Summary: This notice sets forth proposed actions to be taken under the
NIH Guidelines for Research Involving Recombinant DNA Molecules (59 FR
34496). Interested parties are invited to submit comments concerning
these proposals. These proposals will be considered by the Recombinant
DNA Advisory Committee at its meeting on June 8-9, 1995. After
consideration of these proposals and comments by the Recombinant DNA
Advisory Committee, the Director of the National Institutes of Health
will issue decisions in accordance with the NIH Guidelines.
Dates: Comments received by June 1, 1995, will be reproduced and
distributed to the Recombinant DNA Advisory Committee for consideration
at its June 8-9, 1995, meeting.
Addresses: Written comments and recommendations should be submitted to
Dr. Nelson A. Wivel, Director, Office of Recombinant DNA Activities,
National Institutes of Health, MSC 7052, 6006 Executive Boulevard,
Suite 323, Bethesda, Maryland 20892-7052, or sent by FAX to 301-496-
9839.
All comments received in timely response to this notice will be
considered and will be available for public inspection in the above
office on weekdays between the hours of 8:30 a.m. and 5 p.m.
For Further Information Contact: Background documentation and
additional information can be obtained from the Office of Recombinant
DNA Activities, National Institutes of Health, MSC 7052, 6006 Executive
Boulevard, Suite 323, Bethesda, Maryland 20892-7052, Phone 301-496-
9838, FAX to 301-496-9839.
Supplementary Information: The NIH will consider the following actions
under the NIH Guidelines for Research Involving Recombinant DNA
Molecules:
I. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Curiel and Alvarez
In a letter dated January 5, 1995, Drs. David T. Curiel and Ronald
D. Alvarez of the University of Alabama, Birmingham, Alabama, submitted
a human gene transfer protocol entitled: A Phase I Study of Recombinant
Adenovirus Vector-Mediated Delivery of an Anti-erbB-2 Single-Chain
(sFv) Antibody Gene for Previously Treated Ovarian and Extraovarian
Cancer Patients to the Recombinant DNA Advisory Committee for formal
review and approval at its March 6-7, 1995, meeting. Due to reviewers'
comments before the March 1995 meeting, the protocol was not forwarded
to the committee.
In a letter dated April 12, 1995, Drs. David T. Curiel and Ronald
D. Alvarez of the University of Alabama, Birmingham, Alabama, submitted
a revised protocol to the Recombinant DNA Advisory Committee for formal
review and approval at its June 8-9, 1995, meeting.
II. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Curiel
In a letter dated April 13, 1994, Dr. David Curiel of the
University of Alabama, Birmingham, Alabama, submitted the human gene
transfer protocol entitled: Phase I Trial of a Polynucleotide Vaccine
to Human Carcinoembryonic Antigen in Patients with Metastatic
Colorectal Cancer to the Recombinant DNA Advisory Committee for formal
review and approval at its June 9-10, 1994, meeting. During the June
1994 meeting, the committee approved the protocol by a vote of 10 in
favor, 4 opposed, and no abstentions. Approval was contingent on the
review and approval by the primary reviewers of a revised Informed
Consent document (as approved by the Institutional Review Board). On
June 29, Dr. Curiel submitted an Institutional Review Board approved
Informed Consent Document. The primary reviewers approved the revised
[[Page 27207]] Informed Consent Document. On September 17, 1994, Dr.
Nelson Wivel, Office of Recombinant DNA Activities, National Institutes
of Health, informed Dr. Curiel that Dr. Harold Varmus, Director,
National Institutes of Health, concluded that the protocol should be
reviewed again by the committee when additional preclinical data are
available.
In a letter dated April 12, 1995, Dr. David T. Curiel of the
University of Alabama, Birmingham, Alabama, submitted a revised
protocol to the Recombinant DNA Advisory Committee for formal review
and approval at its June 8-9, 1995, meeting.
III. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Drs. Paulson and Lyerly
In a letter dated March 31, 1995, Drs. David F. Paulson and H. Kim
Lyerly of Duke University Medical Center, Durham, North Carolina,
submitted a human gene transfer protocol entitled: A Phase I Study of
Autologous Human Interleukin-2 Gene Modified Tumor Cells in Patients
with Locally Advanced or Metastatic Prostate Cancer to the Recombinant
DNA Advisory Committee for formal review and approval.
IV. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Berchuck and Lyerly
In a letter dated April 10, 1995, Drs. Andres Berchuck and H. Kim
Lyerly of Duke University Medical Center, Durham, North Carolina,
submitted a human gene transfer protocol entitled: A Phase l Study of
Autologous Human Interleukin 2 (IL-2) Gene Modified Tumor Cells in
Patients with Refractory Metastatic Ovarian Cancer to the Recombinant
DNA Advisory Committee for formal review and approval.
V. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Steiner and Holt
On April 13, 1995, Drs. Mitchell S. Steiner and Jeffrey T. Holt of
Vanderbilt University School of Medicine, Nashville, Tennessee,
submitted a human gene transfer protocol entitled: Gene Therapy for the
Treatment of Advanced Prostate Cancer by In Vivo Transduction with
Prostate-Targeted Vectors Expressing Antisense c-myc RNA to the
Recombinant DNA Advisory Committee for formal review and approval.
VI. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. McIvor
In a letter dated April 12, 1995, Dr. R. Scott McIvor of the
Institute of Human Genetics, University of Minnesota, Minneapolis,
Minnesota, submitted a human gene transfer protocol entitled: Gene
Therapy for Purine Nucleoside Phosphorylase Deficiency to the
Recombinant DNA Advisory Committee for formal review and approval.
VII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Drs. Scardino, Thompson, Woo
In a letter dated April 11, 1995, Drs. Peter T. Scardino, Timothy
C. Thompson, and Savio L.C. Woo of Baylor College of Medicine, Houston,
Texas, submitted a human gene transfer protocol entitled: Phase I Study
of Adenoviral Vector Delivery of the HSV-tk Gene and the Intravenous
Administration of Ganciclovir in Men with Local Recurrence of Prostate
Cancer After Radiation Therapy to the Recombinant DNA Advisory
Committee for formal review and approval.
VIII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Dr. Whitley
In a letter dated April 12, 1995, Dr. Chester B. Whitley of the
Institute of Human Genetics, University of Minnesota, Minneapolis,
Minnesota, submitted a human gene transfer protocol entitled: Gene
Therapy for Scheie Keratopathy to the Recombinant DNA Advisory
Committee for formal review and approval.
IX. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Munshi and Barlogie
In a letter dated April 13, 1995, Drs. Nikhil C. Munshi and Bart
Barlogie of the University of Arkansas, Little Rock, Arkansas,
submitted a human gene transfer protocol entitled: Thymidine Kinase
(TK) Transduced Donor Leukocyte Infusions as a Treatment for Patients
with Relapsed or Persistent Multiple Myeloma after T-cell Depleted
Allogeneic Bone Marrow Transplant to the Recombinant DNA Advisory
Committee for formal review and approval.
X. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Fox and Urba
In a letter dated April 12, 1995, Drs. Bernard A. Fox and Walter J.
Urba of Chiles Research Institute, Providence Portland Medical Center,
Portland, Oregon, submitted a human gene transfer protocol entitled:
Adoptive Cellular Therapy of Cancer Combining Direct HLA-B7/2-
Microglobulin Gene Transfer with Autologous Tumor Vaccination for the
Generation of Vaccine-Primed Anti-CD3 Activated Lymphocytes to the
Recombinant DNA Advisory Committee for formal review and approval.
XI. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Hwu
In a letter dated April 12, 1995, Dr. Patrick Hwu of the National
Institutes of Health, Bethesda, Maryland, submitted a human gene
transfer protocol entitled: Treatment of Patients with Advanced
Epithelial Ovarian Cancer using Anti-CD3 stimulated Peripheral Blood
Lymphocytes Transduced with a Gene Encoding a Chimeric T-cell Receptor
Reactive with Folate Binding Protein to the Recombinant DNA Advisory
Committee for formal review and approval.
XII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Dr. Marasco
In a letter dated April 12, 1995, Dr. Wayne A. Marasco of the Dana-
Farber Cancer Institute, Boston, Massachusetts, submitted a human gene
transfer protocol entitled: Intracellular Antibodies Against HIV-1
Envelope Protein for AIDS Gene Therapy to the Recombinant DNA Advisory
Committee for formal review and approval.
XIII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Dr. Verfaillie
In a letter dated April 12, 1995, Dr. Catherine Verfaillie of the
University of Minnesota, Minneapolis, Minnesota, submitted a human gene
transfer protocol entitled: Autologous Marrow Transplantation for
Chronic Myelogenous Leukemia Using Stem Cells Obtained After In Vivo
Chemotherapy Cytokine Priming to the Recombinant DNA Advisory Committee
for formal review and approval.
XIV. Proposed Amendments to Appendix B of the NIH Guidelines Regarding
Updating the Classification of Microorganisms/Fleming
In a letter dated June 24, 1993, Dr. Diane Fleming, President of
the Mid-Atlantic Biological Safety Association requested updating
Appendix B, Classification of Microorganisms on the Basis of Hazard.
The Mid-Atlantic Biological Safety Association submitted an updated
list of the classification of microorganisms for the Committee to
[[Page 27208]] review which included the latest taxonomy and agent risk
group classifications as defined by the Centers for Disease Control and
Prevention. This request was published for public comment in the
Federal Register (August 18, 1994, 58 FR 44098).
During the September 9-10, 1993, meeting, the Recombinant DNA
Advisory Committee recommended by consensus that the current
classification of etiological agents described in the Biosafety in
Microbiological and Biomedical Laboratories, 3rd edition, May 1993,
U.S. Department of Health and Human Services, should be endorsed by the
Committee. The Committee retains the option to adopt any modification
to the CDC listing. The Committee recommended that the revised Appendix
B, Classification of Microorganisms on the Basis of Hazard, submitted
by Dr. Fleming should not be adopted until the Committee received
letters of concurrence from both the Centers for Disease Control and
Prevention and the NIH Division of Safety.
In a telephone call on October 20, 1994, Dr. Fleming stated that
Appendix B, Classification of Microorganisms on the Basis of Hazard,
would be reviewed by experts from the Centers for Disease Control and
Prevention and the American Society for Microbiology. The revised
Appendix B was submitted to the Recombinant DNA Advisory Committee
December 1-2, 1994, meeting for review and discussion. During the
December 1994 meeting, the Committee recommended publishing the revised
Appendix B in the Federal Register for public comment, with further
review of this proposal and possible approval during the March 6-7,
1995, meeting.
During the March 6-7, 1995 meeting, the Recombinant DNA Advisory
Committee deferred approval of the proposed amendments to Appendix B
pending additional revisions to the remaining appendices of the NIH
Guidelines that are required to adequately accommodate the revised
Appendix B. The motion for deferral included a recommendation that a
subcommittee consisting of Dr. Straus, Office of Recombinant DNA
Activities staff, and ad hoc experts would meet for one day to develop
the required modifications. The motion passed by a vote of 17 in favor,
0 opposed, and no abstentions.
The Appendix B Subcommittee met on May 5, 1995. The proposed
Appendix B reads as follows:
Appendix B. Points to Consider in the Assessment of Risk for Research
and Production Involving Human Etiologic Agents and Oncogenic Viruses
Note: Appendix B includes only those biological agents known to
infect humans. Information regarding restricted animal and plant
pathogens is available from: U.S. Department of Agriculture, Animal
and Plant Health Inspection Service, Veterinary Services, Import-
Export Products Staff, Room 756, Federal Building, 6505 Belcrest
Road, Hyattsville, Maryland 20782; Phone: (301) 436-7830; Fax: (301)
436-8226.
Appendix B reflects the current state of knowledge and should be
considered as guidance for establishing an initial, qualitative
assessment regarding the safe handling of specific etiologic agents and
oncogenic viruses and is not intended to replace a thorough assessment
of the potential risk associated with such agents. Although Appendix B
is considered to be comprehensive, this information should not be
considered all-inclusive. A Task Force of the American Society of
Microbiologists (ASM) will conduct an annual review of Appendix B and
its recommendations will be presented to the Recombinant DNA Advisory
Committee (RAC) as proposed amendments to the NIH Guidelines. The
nomenclature reflects conformity with the most recent international
agreements on taxonomy and nomenclature of agents at this time.
Appendix B-I. Qualitative Risk Assessment
Appendix B should be considered in conjunction with Appendices G
and K in making an initial determination regarding the appropriate
level of physical containment necessary to ensure the safe conduct of
research or production. Appendix G specifies physical containment for
standard laboratory experiments involving healthy adult individuals and
defines Biosafety Level 1 (BL1) through Biosafety Level 4 (BL4).
Appendix K supersedes Appendix G for large scale (over 10 liters)
research or production involving healthy adult individuals and defines
Good Large Scale Practice (GLSP) through Biosafety Level 3--Large Scale
(BL3-LS).
Appendix B-II. Quantitative Risk Assessment
Appendix B-II-A. An initial qualitative risk assessment should be
followed by a thorough quantitative risk assessment of the specific
agent strain, immune status of the host relative to the agent in
question, and potential agent-host-activity interactions, e.g.,
potential for aerosol production.
Appendix B-II-B. In the event that additional information is
available regarding a specific strain listed in Appendix B, the
Principal Investigator (PI) must make an initial qualitative risk
assessment. The Institutional Biosafety Committee (IBC) must also make
a quantitative risk assessment for experiments described in Section
III-A, Experiments that Require IBC Approval, RAC Review, and NIH
Approval, and Section III-C, Experiments that Require IBC Approval
Before Initiation.
Appendix B-III. Risk Assessment Criteria
Factors to be considered in determining the level of containment
include agent factors such as: virulence, pathogenicity, stability,
route of spread, communicability, operations(s), quantity, and
availability of vaccines or treatment. Changes to the agent which
enhance or remove virulence factors should be considered by the PI and
IBC which has the authority to raise or lower the containment level for
that particular agent (see Sections III-C-2-a and V-B). For strains in
which there is increased risk potential, the level of physical
containment should be increased over the level that is recommended for
the parent strain.
Appendix B-III-A. Agent-Specific Considerations. The following
criteria should be considered when making a risk assessment
determination for a specific strain:
Appendix B-III-A-1. Any strain isolated directly from a human or
animal should be treated as a potentially pathogenic organism until
proven otherwise.
Appendix B-III-A-2. Any strain that is known to be more hazardous
than the parent (wild-type) strain, e.g., introduction of a drug-
resistance trait to a strain that is not known to acquire that trait
naturally, if such acquisition could compromise the use of the drug to
control that agent, should be handled at a higher containment level
(see Section III-A-1).
Appendix B-III-A-3. For any strain that has been genetically
modified and is not specifically listed in Appendix B, the PI must make
an initial determination regarding the potential risk of the
genetically modified agent. The Institutional Biosafety Committee (IBC)
must also make a quantitative risk assessment for experiments described
in Section III-A, Experiments that Require IBC approval, RAC Review,
and NIH Approval, and Section III-C, Experiments that Require IBC
Approval Before Initiation.
Appendix B-III-A-4. For agents where more than one species is known
[[Page 27209]] to be pathogenic for humans, Appendix B may include the
genus name as well as individual species which are known to be
pathogenic. When such a genus is listed in Appendix B, non-pathogenic
species and strains are excluded. For parasites, non-infectious life
cycle stages are excluded.
Appendix B-III-A-5. Certain attenuated strains or strains that have
been demonstrated to have lost known virulence factors, e.g., genes,
and that are to be used as: (1) a product, (2) part of a product, (3)
or for prophylactic or therapeutic purposes, may qualify for a
reduction in containment compared to the Risk Group (RG) assigned to
the parent strain (see Sections III-C-2-a and V-B).
Appendix B-III-A-6. Careful consideration should be given to the
application of some Risk Group 2 (RG2) agents. RG2 agents may be
cultured at BL2 containment, e.g., dengue virus; however, when such
agents are used for animal inoculation work or transmission studies,
BL3 containment is recommended. Similarly, RG3 agents, e.g., monkey
pox, Venezuelan equine encephalitis, and yellow fever viruses should be
handled at BL4 containment for animal inoculation and transmission
studies.
Appendix B-III-A-7. Individuals working with HIV, SIV, or other
bloodborne pathogens should consult the Occupational Exposure to
Bloodborne Pathogens, Final Rule (see Appendix B-VI-J). BL2 containment
is recommended for activities involving all blood-contaminated clinical
specimens, body fluids, and tissues from all humans or from HIV- or
SIV- infected or inoculated laboratory animals. Activities such as
producing research-laboratory scale quantities of HIV or SIV,
manipulating concentrated virus preparations, and conducting procedures
that may produce droplets or aerosols, are performed in a BL2 facility,
but using the additional practices and containment equipment
recommended for BL3. Activities involving industrial-scale volumes or
preparation of concentrated HIV or SIV are conducted in a BL3 facility,
using BL3 practices and containment equipment (see Appendix B-VI-D).
Appendix B-III-A-8. Specific strains may fall into either a more
hazardous Risk Group (RG) or a less hazardous risk group depending on
genetic background and natural history. Appendix B is derived from
information regarding the parent (wild-type) strain (see Appendices B-
VI-B through B-VI-D).
Appendix B-III-B. Laboratory Personnel Considerations. Appendix B
is based on the potential effect of a biological agent on healthy adult
humans and does not account for instances in which an individual may
have increased susceptibility to such agents, e.g., preexisting
disease, medications, compromised immunity, pregnancy, or breast
feeding.
Appendix B-IV. Classification of Etiologic Agents and Oncogenic Viruses
by Risk Group (RG)
The World Health Organization recommends the use of the term Risk
Group (RG) to indicate qualitative risk assessment based on agent
characteristics (see Appendix B-VI-E). Appendix B is intended to serve
as guidance in determining RG classification. The characteristics used
for the qualitative risk assessment of biohazardous agents by RG are
defined in Appendix B-IV-A. RG are categorized according to their
potential risk, i.e., Risk Group 1 (RG1) corresponds to the lowest
level of risk and Risk Group 4 (RG4) corresponds to the highest level
of risk (see Appendix B-VI-E). Appendix B-IV-B summarizes RG1 through
RG4 and the relationship of these categories to Appendix G (see
Appendix B-VI-E).
Certain strains specified in RG2, are known to represent minimal
risk to humans; therefore, such organisms may be classified within RG1
and handled at BL1 (see Appendices III-C-2-a and V-B). Certain
attenuated strains that are commonly used for live vaccines or that
have an extensive history of safe laboratory use without harmful
effect, may be placed in a lower RG than the parent strain (see
Appendices B-VI-C and B-VI-D).
Risk assessment is ultimately a subjective process. Strains that
are not listed in RG2 through RG4 are not implicitly classified in RG1;
therefore, the PI must make an initial risk assessment determination.
The Institutional Biosafety Committee (IBC) must also make a
quantitative risk assessment for experiments described in Section III-
A, Experiments that Require IBC approval, RAC Review, and NIH Approval,
and Section III-C, Experiments that Require IBC Approval Before
Initiation. Further guidance regarding the assessment of risk for
agents not specifically listed in Appendix B is available from: Centers
for Disease Control and Prevention, Biosafety Branch, Office of Health
and Safety, Mail Stop F-05, 1600 Clifton Road, N.E., Atlanta, Georgia
30333; Phone: (404) 639-3883; Fax: (404) 639-2294. Biosafety in
Microbiological and Biomedical Research Laboratories (see Appendix B-
VI-D) and Control of Communicable Diseases in Man (see Appendix B-VI-B)
provide additional guidance for determining appropriate containment
conditions for specific etiologic agents and oncogenic viruses.
Appendix B-IV-A. Classification of Biohazardous Agents by Risk
Group (RG) (see Appendix B-VI-E).
Appendix B-IV-A--Classification of Biohazardous Agents by Risk Group (RG)
Risk Group 1 (RG1)........ No/very low individual risk.... An agent that is unlikely to cause human disease.
No/very low community risk..... Well characterized agents not known to cause
disease in healthy adult humans and of minimal
potential hazard to laboratory personnel and the
environment.
Risk Group 2 (RG2)........ Moderate individual risk....... Agents which can cause human disease but are
Low community risk............. unlikely to be a serious hazard to workers, the
community or the environment; percutaneous
exposure, ingestion, or mucous membrane exposure
may cause serious infection; however, effective
treatment and preventive measures are available
and the risk of spread of infection is limited.
Risk Group 3 (RG3)........ High individual risk........... Indigenous or exotic agents which usually cause
Low community risk............. serious human disease but do not ordinarily spread
from one infected individual to another. Effective
treatment or preventive measures are available.
Risk Group 4 (RG4)........ High individual risk........... Dangerous/exotic agents which can cause serious
High community risk............ human disease and can be readily transmitted
directly or indirectly from one individual to
another. Effective treatment and preventive
measures are not usually available.
[[Page 27210]]
Appendix B-IV-B. Relationship Between Risk Group (RG) and Appendix
G (see Appendix B-VI-E).
Note. Special consideration will be given to large-scale
(greater that 10 liters of culture) and aerosol producing operations
which may pose additional significant risks and thus may require
additional containment (see Appendix K).
Appendix B-IV-B--Relationship Between Risk Group (RG) and Appendix G (see Appendix B-VI-E)
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Examples of
Risk group (RG) Biosafety level laboratories Laboratory practices Safety equipment
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Risk Group 1 (RG1). Biosafety Level 1 Basic teaching Good microbiological Generally not required
(BL1) (Appendix G- laboratories. practices (Appendix G- (Appendix G-II-A-4).
II-A). II-A-1).
Risk Group 2 (RG2). Biosafety Level 2 (1) primary health Good microbiological Open bench plus
(BL2) (Appendix G- services; (2) primary practices, protective biosafety cabinet
II-B). level hospitals; (3) clothing, biosafety (Class I,II) for
diagnostic, teaching, sign when special potential aerosols
and research provisions required (Appendices G-II-B-3
laboratories. (Appendix G-II-B-2). and G-III-L).
Risk Group 3 (RG3). Biosafety Level 3 Special diagnostic Good microbiological Biosafety cabinet
(BL3) (Appendix G- laboratories. practices, protective (Class I,II,II) and/
II-C). clothing, biosafety or other primary
sign, special containment for all
clothing, controlled activities
assess, directional (Appendices G-II-C-3
air flow (Appendix G- and G-III-L).
II-C-2).
Risk Group 4 (RG4). Maximum Containment/ Dangerous pathogens Good microbiological Biosafety cabinet
Biosafety Level 4 units. practices, protective (Class III) or Class
(BL4) (Appendix G- clothing, biosafety I or II in
II-D). sign, special combination with
clothing, controlled positive pressure
assess, directional suits ventilated by
air flow, airlock life-support system,
entry, shower exit, double-door autoclave
special waste (Appendices G-II-D-4
disposal (Appendix G- and G-II-L).
II-D-2).
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Appendix B-IV-C. Risk Group 1 (RG1) Agents
Note. It is not appropriate to assume that an unassessed agent
belongs in RG1, e.g., vaccine strains which have undergone multiple
in vivo passages are not considered to be avirulent based only on
the fact that they are vaccine strains.
RG1 agents are usually not placed on a list but are assumed to
include all bacterial, fungal, viral, rickettsial, chlamydial, and
parasitic agents which have been assessed for hazard and that are not
included in higher RG. RG1 agents can be used for undergraduate and
secondary educational training and teaching laboratories and other
facilities in which work is conducted with defined and characterized
strains of viable microorganisms that are: (1) not known to cause
disease in healthy adult humans, and (2) represent minimal potential
hazard to laboratory personnel or the environment under standard
conditions. RG1 agents can be handled safely in the laboratory without
special apparatus or equipment using techniques generally acceptable
for nonpathogenic materials. RG1 includes the following agents:
asporogenic Bacillus subtilis or Bacillus licheniformis (see exceptions
in Appendix C-IV-A); Escherichia coli-K12 (see exceptions in Appendix
C-II-A); Saccharomyces cerevisiae and Saccharomyces uvarum (see
exceptions in Appendix C-III-A); Baculovirus vectors (see exceptions in
Appendix C-I-A); infectious canine hepatitis viruses; and influenza
reference strains A/PR/8/34 and A/WS/33.
Appendix B-IV-C-1. Risk Group 1 (RG1) Low-Risk Oncogenic Viruses (See
Appendix B-VI-G)
Adenovirus 7-Simian virus 40 (Ad7-SV40)
Avian leukosis virus
Bovine leukemia virus
Bovine papilloma virus
Chick-embryo-lethal orphan (CELO) virus or fowl adenovirus 1
Dog sarcoma virus
Guinea pig herpes virus
Lucke (Frog) virus
Hamster leukemia virus
Marek's disease virus
Mason-Pfizer monkey virus
Mouse mammary tumor virus
Murine leukemia virus
Murine sarcoma virus
Polyoma virus
Rat leukemia virus
Rous sarcoma virus
Shope fibroma virus
Shope papilloma virus
Simian virus 40 (SV40)
Appendix B-IV-D. Risk Group 2 (RG2) Agents
RG2 includes agents that represent moderate risk to healthy human
adults and the environment. RG2 agents may produce disease (varying
degrees of severity) as a result of accidental inoculation, injection,
or other means of cutaneous penetration. RG2 agents can generally be
contained using standard laboratory practices. Some RG2 agents may
cause disease as a result of direct contact or respiratory
transmission; however, such instances are self-limiting and do not
result in serious illness, e.g. the common cold (rhinoviruses). RG2
agents are recommended for use only in facilities where laboratory
personnel are trained in the safe handling of these agents (see
Appendix G-II-B-2).
Appendix B-IV-D-1. Risk Group 2 (RG2)--Bacteria
Note. When ``spp'' follows the name of a genus, or ``serotype''
follows a species, only those species or serotypes known to be
pathogenic to healthy human adults are included.
Acinetobacter baumannii
Actinobacillus spp.
Actinomyces pyogenes
Aeromonas hydrophila
Amycolata autotrophica
Archanobacterium haemolyticum
Arizona hinshawii--all serotypes
Bacillus anthracis (BL3 practices)
Bartonella henselae, B. quintana, B. vinsonii
Bordetella spp. including B. pertussis (BL3 practices)
Borrelia recurrentis, B. burgdorferi
Burkholderia (previously Pasteurella spp.) except those listed in
Appendix B-IV-E-1 (RG3))
Burkholderia pseudomallei (BL3 practices)
Campylobacter coli, C. fetus spp. fetus, C. jejuni
Chlamydia psittaci (BL3 practices)
Chlamydia trachomatis (BL3 practices)
Chlamydia pneumoniae (BL3 practices)
Clostridium botulinum (BL3 practices), Cl. chauvoei, Cl. haemolyticum,
Cl. [[Page 27211]] histolyticum, Cl. novyi, Cl. septicum, Cl. tetani
Corynebacterium diphtheriae, C. pseudotuberculosis, C. renale
Dermatophilus congolensis
Edwardsiella tarda
Erysipelothrix rhusiopathiae
Escherichia coli--all enteropathogenic, enterotoxigenic, enteroinvasive
and strains bearing K1 antigen, including E. coli O157:H7
Haemophilus ducreyi, H. influenzae
Helicobacter pylori
Klebsiella spp.
Legionella spp. including L. pneumophila (BL3 practices)
Legionella-like organisms
Leptospira interrogans--all serotypes
Listeria spp.
Moraxella spp.
Mycobacterium spp. (except those listed in Appendix B-IV-E-1 (RG3))
including M. avium complex, M. asiaticum, M. chelonei, M. fortuitum, M.
kansasii, M. leprae, M. malmoense, M. marinum, M. paratuberculosis, M.
scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi
Mycoplasma spp., except M. mycoides and M. agalactiae which are
restricted animal pathogens (see Appendix B-V-B)
Neisseria gonorrhoea (BL3 practices), N. meningitidis (BL3 practices)
Nocardia asteroides, N. brasiliensis, N. otitidiscaviarum, N.
transvalensis Rhodococcus equi
Salmonella spp. and serotypes including S. arizonae, S. cholerasuis, S.
enteritidis, S. gallinarum-pullorum, S. meleagridis, S. paratyphi, A,
B, C, S. typhi (BL3 practices), S. typhimurium
Shigella spp. (BL3 practices) and serotypes including S. boydii, S.
dysenteriae, Type 1, S. flexneri, S. sonnei
Sphaerophorus necrophorus
Staphylococcus aureus
Streptobacillus moniliformis
Streptococcus spp. including Streptococcus pneumoniae, S. pyogenes
Treponema pallidum, T. carateum
Vibrio cholerae, V. parahemolyticus, V. vulnificus
Yersinia enterocolitica, Y. pestis (BL3 practices)
Appendix B-IV-D-2. Risk Group 2 (RG2)--Fungal Agents
Note. When ``spp'' follows the name of a genus, or ``serotype''
follows a species, only those species or serotypes known to be
pathogenic to healthy human adults are included.
Blastomyces dermatitidis
Cladosporium bantianum, C. (Xylohypha) trichoides
Cryptococcus neoformans (Droplets/aerosols require biosafety cabinet)
Dactylaria galopava (Ochroconis gallopavum)
Epidermophyton spp.
Exophiala (Wangiella) dermatitidis
Fonsecaea pedrosoi
Microsporum spp.
Paracoccidioides braziliensis
Penicillium marneffei
Sporothrix schenckii
Trichophyton spp.
Appendix B-IV-D-3. Risk Group 2 (RG2)--Parasitic Agents
Note. When ``spp'' follows the name of a genus, or ``serotype''
follows a species, only those species or serotypes known to be
pathogenic to healthy human adults are included.
Ancylostoma spp. human hookworms including A. duodenale, A. ceylanicum
Ascaris spp. including Ascaris lumbricoides suum
Babesia spp. including B. divergens, B. microti
Brugia spp. filaria worms including B. malayi, B. timori
Coccidia spp.
Cryptosporidium spp. including C. parvum
Cysticercus cellulosae (hydatid cyst, larva of T. solium)
Echinococcus spp. including E. granulosis, E. multilocularis, E. vogeli
Entamoeba histolytica
Enterobius spp.
Fasciola spp. including F. gigantica, F. hepatica
Giardia spp. including G. lamblia
Heterophyes spp.
Hymenolepis spp. including H. diminuta, H. nana
Isospora spp.
Leishmania spp. including L. braziliensis, L. donovani, L. ethiopia, L.
major, L. mexicana, L. peruvania, L. tropica
Loa loa filaria
Microsporidium spp.
Naegleria fowleri
Necator spp. human hookworms, including N. americanus
Onchoerca spp. filaria including, O. volvulus
Plasmodium spp. including simian species, P. cynomologi, P. falciparum,
P. malariae, P. ovale, P. vivax
Sarcocystis spp. including S. sui hominis
Schistosoma spp. including S. haematobium, S. intercalatum, S.
japonicum, S. mansoni, S. mekongi
Strongyloides spp. including S. stercoralis
Taenia solium
Toxocara spp. including T. canis
Toxoplasma spp. including T. gondii
Trichinella spiralis
Trypanosoma spp. including T. brucei brucei, T. brucei gambiense, T.
brucei rhodesiense, T. cruzi
Wuchereria bancrofti (filaria)
Appendix B-IV-D-4-a. Risk Group 2 (RG2)--Viruses and Prions (See
Appendices B-IV-D-4-b and B-IV-D-4-c)
Note. When ``spp'' follows the name of a genus, or ``serotype''
follows a species, only those species or serotypes known to be
pathogenic to healthy human adults are included.
Adenoviruses, human--all types
Arboviruses (see Appendix B-IV-D-4-b)
Arenaviruses (see Appendix B-IV-D-4-b)
Bunyamwera virus
Coronaviruses
Coxsackie A and B viruses
Creutzfeldt-Jacob disease agent (prion)
Echoviruses--all types
Encephalomyocarditis virus (EMC)
Encephalomyelitis viruses (droplets/aerosols require BL3 practices)
(see Appendix B-IV-D-4-b)
Hepatitis A, B (BL3 practices), C (BL3 practices), D, E viruses
Herpesviruses (BL3 practices) including Cytomegalovirus, Epstein Barr,
Herpes simplex types 1 and 2, and Herpes zoster, except Herpesvirus
simiae (Monkey B virus) (see Appendix B-IV-F-4 (RG4))
Human Immunodeficiency Virus (HIV) all serotypes (see Appendices B-VI-
A-7 and B-IV-J for special requirements)
Human T cell lymphotropic viruses (HTLV) types 1 and 2 (BL3 practices)
Influenza viruses
Kuru (prion)
Lymphocytic choriomeningitis virus (BL3 practices--except neurotropic
strains)
Lymphogranuloma venereum agent
Measles virus
Molluscum contagiosum virus
Mumps virus
Orf virus
Papovaviridae including human papilloma viruses
Parainfluenza virus
Paravaccinia virus
Polioviruses--all types, wild and attenuated
Poxviruses--all types such as Cowpox (biosafety cabinet and
immunization required), Monkeypox (biosafety cabinet and immunization
required) or Vaccinia (biosafety cabinet and immunization required),
Camelpox, Milkers node virus, Molluscum contagiosum virus, Orf,
Rabbitpox, Tanapox, and Yabapox except Alastrim, Smallpox, and Whitepox
(see Appendices B-V-B and B-VI-H) [[Page 27212]]
Rabies virus (biosafety cabinet and immunization required)--all strains
including
fixed/attenuated virus
except Rabies street virus
Reoviruses--all types
Respiratory syncytial virus
Rhinoviruses--all types
Rubella virus
Simian viruses--all types including simian immunodeficiency virus (BL3
practices), except Herpesvirus simiae (Monkey B virus) and Marburg
virus (see Appendix B-IV-F-4 (RG4))
Transmissible Spongioform Encephalopathies (TME)--prions (Creutzfieldt-
Jacob; Kuru)
Vesicular Stomatitis Virus, lab adapted strains: VSV-Indiana, San Juan,
and Glasgow
Appendix B-IV-D-4-b. Arboviruses and Arenaviruses Assigned to Biosafety
Level 2
Note. When laboratory work is conducted with biological agents
for which epidemiology and etiology are unknown or incompletely
understood, it is presumed that the work presents a biohazard
similar to related agents until further information can be provided.
This method of risk assessment was used by the American Committee on
Arthropod-Borne Viruses (ACAV) Subcommittee on Arbovirus Laboratory
Safety for work with arboviruses for which risk information is
inadequate or unavailable (see Appendix B-VI-D).
Acado
Acara
Aguacate
Alfuy
Almpiwar
Amapari
Ananindeua
Anhanga
Anhembi
Anopheles A
Anopheles B
Apeu
Apoi
Aride
Arkonam
Aroa
Aruac
Arumowot
Aura
Avalon
Abras
Abu Hammad
Aabahoyo
Bagaza
Bahig
Bakau
Baku
Bandia
Bangoran
Bangui
Banzi
Barmah Forest
Barur
Batai
Batama
Bauline
Bebaru
Belmont
Benevides
Benfica
Bertioga
Bimiti
Birao
Bluetongue
Boraceia
Botambi
Boteke
Bouboui
Bujaru
Bunyamwera
Bunyip
Burg E Arab
Bushbush
Bussuquara
Buttonwillow
Bwamba
Cacao
Cache Valley
Caimito
California enc.
Calovo
Candiru
Cape Wrath
Capim
Caraparu
Carey Island
Catu
Chaco
Chagres
Chandipura
Changuinola
Charleville
Chenuda
Chilibre
Chobar gorge
Clo Mor
Colorado tick fever
Corriparta
Cotia
Cowbone Ridge
Csiro Village
Cuiaba-D'aguilar
Dakar Bat
Dengue-1
Dengue-2
Dengue-3
Dengue-4
Dera Ghazi Khan
East. equine enc. (vaccine recommended)
Edge Hill
Entebbe Bat
Ep. Hem. Disease
Erve
Eubenangee
Eyach
Flanders
Fort Morgan
Frijoles
Gamboa
Gan Gan
Gomoka
Gossas
Grand Arbaud
Great Island
Guajara
Guama
Guaratuba
Guaroa
Gumbo Limbo
Hart Park
Hazara
Highlands J
Huacho
Hughes
Icoaraci
Ieri
Ilesha
Ilheus
Ingwavuma
Inkoo
Ippy
Irituia
Isfahan
Itaporanga
Itaqui
Jamestown Canyon
Japanaut
Jerry Slough
Johnston Atoll
Joinjakaka
Juan Diaz
Jugra
Jurona
Jutiapa
Kadam
Kaeng Khoi
Kaikalur
Kaisodi
Kamese
Kammavan pettai
Kannaman galam
Kao Shuan
Karimabad
Karshi
Kasba
Kemerovo
Kern Canyon
Ketapang
Keterah
Keuraliba
Keystone
Kismayo
Klamath
Kokobera
Kolongo
Koongol
Kotonkan
Kowanyama
Kunjin
Kununurra
Kwatta
La Crosse
La Joya
Lagos Bat
Landjia
Langat
Lanjan
Las Maloyas
Latino
Le Dantec [[Page 27213]]
Lebombo
Lednice
Lipovnik
Lokern
Lone Star
Lukuni
M'poko
Madrid
Maguari
Mahogany Hammock
Main Drain
Malakal
Manawa
Manzanilla
Mapputta
Maprik
Marco
Marituba
Marrakai
Matariya
Matruh
Matucare
Melao
Mermet
Minatitlan
Minnal
Mirim
Mitchell River
Modoc
Moju
Mono Lake
Mont. myotis leuk.
Moriche
Mosqueiro
Mossuril
Mount Elgon Bat
Murutucu
Mykines
Navarro
Nepuyo
Ngaingan
Nique
Nkolbisson
Nola
Ntaya
Nugget
Nyamanini
Nyando
O'nyong-nyong
Okhotskiy
Okola
Olifantsvlei
Oriboca
Ossa
Pacora
Pacui
Pahayokee
Palyam
Parana
Pata
Pathum Thani
Patois
Phnom-Penh Bat
Pichinde
Pixuna
Pongola
Ponteves
Precarious Point
Pretoria
Prospect Hill
Puchong
Punta Salinas
Punta Toro
Qalyub
Quaranfil
Restan
Rio Bravo
Rio Grande
Ross River
Royal Farm
Sabo
Saboya
Saint Floris
Sakhalin
Salehabad
San angelo
Sandfly f. (Naples)
Sandfly f. (Sicilian)
Sandjimba
Sango
Sathuperi
Sawgrass
Sebokele
Seletar
Sembalam
Serra do Navio
Shamonda
Shark River
Shuni
Silverwater
Simbu
Simian hem. fever
Sindbis
Sixgun City
Snowshoe Hare
Sokuluk
Soldado
Sororoca
Stratford
Sunday Canyon
Tacaiuma
Tacaribe
Taggert
Tahyna
Tamiami
Tanga
Tanjong Rabok
Tataguine
Tehran
Tembe
Tembusu
Tensaw
Tete
Tettnang
Thimiri
Thottapalayam
Tibrogargan
Timbo
Timboteua
Tindholmur
Toscana
Toure
Tribec
Triniti
Trivittatus
Trubanaman
Tsuruse
Turlock
Tyuleniy
Uganda S
Umatilla
Umbre
Una
Upolu
Urucuri
Usutu
Uukuniemi
Vellore
Venkatapuram
Vinces
Virgin River
VS-Indiana
VS-New Jersey
Wad Medani
Wallal
Wanowrie
Warrego
West. equine enc. (vaccine recommended)
Whataroa
Witwatersrand
Wonga
Wongorr
Wyeomyia
Yaquinea Head
Yata
Yogue
Zaliv Terpeniya
Zegla
Zika
Zingilamo
Zirqa
Appendix B-IV-D-4-c. Vaccine Strains of Risk Group 3 (RG3) and Risk
Group 4 (RG4) Viruses Which May Be Handled at Biosafety Level 2
Chikungunya, strain 131/25
Junin, strain Candid #1
Rift Valley fever, strain MP-12
Venezuelan equine encephalomyelitis, strain TC-83
Yellow fever, strain 17-D
Appendix B-IV-D-4-d. Risk Group 2 (RG2)--Moderate Risk Oncogenic
Viruses (see Appendix B-VI-G)
Adenovirus
Adenovirus 2--simian virus 40 (Ad2-SV40)
Epstein Barr virus (EBV)
Feline leukemia virus (FeLV)
Feline sarcoma virus (FeSV)
Gibbon leukemia virus (GaLV)
Herpesvirus (HV) ateles
Herpesvirus (HV) saimiri
Papovaviridae including human papilloma viruses
Simian sarcoma virus (SSV)-1
Yabapox virus
Appendix B-IV-E. Risk Group 3 (RG3) Agents
Note. When ``spp'' follows the name of a genus, or ``serotype''
follows a species, only those species or serotypes known to be
pathogenic to healthy human adults are included.
[[Page 27214]]
RG3 includes indigenous or exotic agents which may potentially
cause serious or lethal disease as a result of inhalation exposure. RG3
includes agents involving special hazards to laboratory personnel or
agents derived from outside the United States and require a permit for
importation, unless they are specified for higher classification. RG3
includes pathogens which require special containment conditions for
facilities in which laboratory personnel have received specialized
training in: (1) the safe handling of hazardous agents, i.e., equal to
or greater than college level microbiology laboratory training, and (2)
handling the specific RG3 agent or similar pathogens that may
potentially cause serious or lethal disease. Laboratory personnel shall
be supervised by trained scientists who possess significant experience
in the safe handling of biohazardous agents and materials.
Appendix B-IV-E-1. Risk Group 3 (RG3)--Bacterial Agents including
Chlamydia and Rickettsia
Bartonella spp.
Brucella spp. including B. abortus, B. canis, B. melitensis (USDA
restricted), B. suis
Burkholderia (Pseudomonas) mallei, B. pseudomallei (see Appendix B-VI-
F)
Coxiella burnetii
Francisella tularensis
Mycobacterium bovis, M. tuberculosis
Pasteurella multocida type B--``buffalo'' and others (see Appendix B-
VI-F)
Rickettsia akari, R. australis, R. canada, R. conorii, R. prowazekii
R. rickettsii, R, siberica, R. tsutsugamushi, R. typhi (R. mooseri)
Yersinia pestis (antibiotic resistant strains)
Appendix B-IV-E-2. Risk Group 3 (RG3)--Fungal Agents
Coccidioides immitis (sporulating cultures; contaminated soil)
Histoplasma capsulatum, H. capsulatum var. duboisii
Appendix B-IV-E-3. Risk Group 3 (RG3)--Parasitic Agents
None
Appendix B-IV-E-4. Risk Group 3 (RG3)--Viral Agents
Arboviruses and certain other viruses assigned to Risk Group 3
(West Nile and Semliki Forest viruses may be classified up or down
depending on the conditions of use and geographical location of the
laboratory (see Appendices B-IV-E-5, B-IV-E-6 and B-VI-I).
Lymphocytic choriomeningitis virus (LCM) (neurotrophic strains)
Monkey pox virus--when used in vitro (see Appendix B-VI-H)
Rabies Street virus
Appendix B-4-E-5. Arboviruses and Certain Other Viruses Assigned to
Biosafety Level 3 (on the Basis of Insufficient Experience)
Adelaide River
Agua Preta
Alenquer
Almeirim
Altamira
Andasibe
Antequera
Araguari
Aransas Bay
Arbia
Arboledas
Babanki
Batken
Belem
Berrimah
Bimbo
Bobaya
Bobia
Bozo
Buenaventura
Cabassue (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Cacipacore
Calchaqui
Cananeia
Caninde
Chim
Coastal Plains
Connecticut
Corfou
Dabakala
Douglas
Enseada
Estero Real
Fomede
Forecariah
Fort Sherman
Gabek Forest
Gadgets Gully
Garba
Gordil
Gray Lodge
Gurupi
Iaco
Ibaraki
Ife
Ingangapi
Inini
Issyk-Kul
Itaituba
Itimirim
Itupiranga
Jacareacanga
Jamanxi
Jari
Kedougou
Khasan
Kindia
Kyzylagach
Lake Clarendon
Llano Seco
Macaua
Mapuera
Mboke
Meaban
Mojui Dos Compos
Monte Dourado
Munguba
Naranjal
Nariva
Nasoule
Ndelle
New Minto
Ngari
Ngoupe
Nodamura
Northway
Odrenisrou
Omo
Oriximina
Ouango
Oubangui
Oubi
Ourem
Palestina
Para
Paramushir
Paroo River
Perinet
Petevo
Picola
Playas
Pueblo Viejo
Purus
Radi
Razdan
Resistencia
Rochambeau
Salanga
San Juan
Santa Rosa
Santarem
Saraca
Saumarez Reef
Sedlec
Sena Madureira
Sepik
Shokwe
Slovakia
Somone
Spipur
Tai
Tamdy
Telok Forest
Termeil
Thiafora
Tilligerry
Tinaroo
Tlacotalpan
Tonate (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Ttinga
Xiburema
Yacaaba
Yaounde
Yoka
Yug Bogkanova
Appendix B-IV-E-6. Arboviruses and Certain Other Viruses Assigned to
Biosafety Level 3
Aino [[Page 27215]]
Akabane
Bhanja
Chikungunya (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Cocal
Dhori
Dugbe
Everglades (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Flexal
Germiston (BL3 facilities/HEPA filtration of exhaust air prior to
discharge)
Getah
Hantaan
Israel Turkey mening.
Japanese enc.
Junin (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Kairi
Kimberley
Koutango
Louping Ill (BL3 facilities/HEPA filtration of exhaust air prior to
discharge) (The importation, possession, or use of this agent is
restricted by USDA regulation or administrative policy) (see Appendices
B-VI-D and B-VI-F)
Mayaro
Middelburg
Mobala
Mopeia (This virus is presently being registered in the Catalogue of
Arboviruses)
Mucambo (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Murray Valley enc.
Nairobi sheep disease (The importation, possession, or use of this
agent is restricted by USDA regulation or administrative policy) (see
Appendices B-VI-D and B-VI-F).
Ndumu
Negishi
Oropouche (BL3 facilities/HEPA filtration of exhaust air prior to
discharge)
Orungo
Peaton
Piry
Powassan
Puumala
Rift Valley fever (Zinga virus) (BL3 facilities/HEPA filtration of
exhaust air prior to discharge, vaccine recommended) The importation,
possession, or use of this agent is restricted by USDA regulation or
administrative policy (see Appendices B-VI-D and B-VI-F).
Sagiyama
Sal Vieja
San Perlita
Semliki Forest
Seoul
Spondweni
St. Louis enc.
Thogoto
Tocio (BL3 facilities/HEPA filtration of exhaust air prior to
discharge)
Turuna
Venezuelan equine encephalitis (BL3 facilities/HEPA filtration of
exhaust air prior to discharge, vaccine recommended)
Vesicular Stomatitus (alagoas)
Wesselsbron (BL3 facilities/HEPA filtration of exhaust air prior to
discharge) (The importation, possession, or use of this agent is
restricted by USDA regulation or administrative policy) (see Appendices
B-VI-D and B-VI-F).
West Nile
Yellow fever (BL3 facilities/HEPA filtration of exhaust air prior to
discharge, vaccine recommended)
Zinga (Rift Valley Fever virus) (BL3 facilities/HEPA filtration of
exhaust air prior to discharge, vaccine recommended) The importation,
possession, or use of this agent is restricted by USDA regulation or
administrative policy (see Appendices B-VI-D and B-VI-F).
Appendix B-IV-F. Risk Group 4 (RG4) Agents
RG4 includes dangerous and exotic agents that pose a high
individual risk of aerosol-transmitted laboratory infections (or
related agents with unknown means of transmission) which can result in
life-threatening disease. RG4 agents require the most stringent
containment conditions because they are extremely hazardous to
laboratory personnel and may cause serious epidemic disease. RG4 agents
can only be used in special facilities in which laboratory personnel
have received specialized training in: (1) the safe handling of
hazardous agents, i.e., equal to or greater than college level
microbiology laboratory training, and (2) handling the specific RG3
agent or similar pathogens that may potentially cause serious or lethal
disease. Laboratory personnel shall be supervised by trained scientists
who possess significant experience in the safe handling of biohazardous
agents and materials.
Appendix B-IV-F-1. Risk Group 4 (RG4)--Bacterial Agents
None
Appendix B-IV-F-2. Risk Group 4 (RG4)--Fungal Agents
None
Appendix B-IV-F-3. Risk Group 4 (RG4)--Parasitic Agents
None
Appendix B-IV-F-4. Risk Group 4 (RG4)--Viral Agents
Absettarov
Central European encephalitis viruses
Crimean hemorrhagic fever (Congo)
Ebola fever virus
Guanarito
Hanzalova
Hemorrhagic fever agents and viruses as yet undefined
Herpesvirus simiae (Monkey B virus)
Hypr
Junin (BL3 containment and practices if vaccinated)
Kumlinge
Kyasanur forest disease
Lassa
Machupo
Marburg
Omsk hemorrhagic fever
Russian spring--summer encephalitis
Tick-borne orthomyxoviridae, Dhori & Thogoto
Appendix B-V. Restricted Pathogens
Appendix B-V-A. Restricted Plant Pathogens
Note. See Appendix P, Physical and Biological Containment for
Recombinant DNA Research Involving Plants.
Non-indigenous plant pathogens may require special laboratory
design, operation, and containment features not generally addressed in
Biosafety in the Microbiological and Biomedical Research Laboratories
(see Appendix B-VI-D). Information on the importation, possession, or
use of these agents is available from: U.S. Department of Agriculture,
Animal and Plant Health Inspection Service, Veterinary Services,
Import-Export Products Staff, Room 756, Federal Building, 6505 Belcrest
Road, Hyattsville, Maryland 20782; Phone: (301) 436-7830; Fax: (301)
436-8226.
Appendix B-V-B. Restricted Animal Pathogens
Note. See Appendix Q, Physical and Biological Containment for
Recombinant DNA Research Involving Animals.
Non-indigenous domestic livestock and poultry pathogens may require
special laboratory design, operation, and containment features not
generally addressed in Biosafety in the Microbiological and Biomedical
Research Laboratories (see Appendix B-VI-D). The importation,
possession, or use of these agents is prohibited or restricted by law
or by the U.S. Department of Agriculture regulations and administrative
policies. Animal pathogens other than those zoonotic
[[Page 27216]] agents listed in Appendix B may be subject to USDA
regulations. Information on the importation, possession, or use of
these agents is available from: U.S. Department of Agriculture, Animal
and Plant Health Inspection Service, Veterinary Services, Import-Export
Products Staff, Room 756, Federal Building, 6505 Belcrest Road,
Hyattsville, Maryland 20782; Phone: (301) 436-7830; Fax: (301) 436-
8226.
Appendix B-V-C. Organisms Which May Not Be Studied in the United States
Except at Specified Facilities
Alastrim (see Appendix B-VI-H)
Small pox (see Appendix B-VI-H)
White pox (see Appendix B-VI-H)
Appendix B-VI. Footnotes and References to Appendix B
Appendix B-VI-A. Appendix B has been adapted from the RG
classification recommended by the World Health Organization (see
Appendix B-VI-E), the Agent Summary Statements described in Biosafety
in Microbiological and Biomedical Laboratories (see Appendix B-VI-D),
Control of Communicable Diseases of Man (see Appendix B-VI-B),
recommendations of the Task Force of the American Society for
Microbiology, and a 1982 draft document of the Centers for Disease
Control and Prevention, which includes a more complete risk assessment
of human pathogens (Dr. R. Knudsen--personal communication). Appendices
B-IV-A and B-IV-B are derived from the World Health Organization
Laboratory Biosafety Manual (see Appendix B-VI-E). Appendices B-IV-D-4-
b, B-IV-D-4-c, B-IV-E-5 and B-IV-E-6 were obtained directly (electronic
transmission) from the Centers for Disease Control and Prevention. The
original reference for this classification was Classification of
Etiologic Agents on the Basis of Hazard, 4th edition, July 1974 (see
Appendix B-VI-C).
Appendix B-VI-B. Benenson, Abram S. ed., Control of Communicable
Diseases in Man, 15th edition. 1990. American Public Health
Association, Washington, D.C.
Appendix B-VI-C. Center for Disease Control, Office of Biosafety,
Classification of Etiologic Agents on the Basis of Hazard, 4th Edition.
1974. U.S. Department of Health, Education and Welfare, Public Health
Service.
Appendix B-VI-D. U.S. Department of Health and Human Services,
Public Health Service, Centers for Disease Control and Prevention and
the National Institutes of Health. Biosafety in Microbiological and
Biomedical Research Laboratories, 3rd edition. 1993. Copies available
from: Superintendent of Documents, U.S. Government Printing Office,
Washington, D.C. 20402 (stock # 017-040-00523-7), Phone: (202) 512-
2356.
Appendix B-VI-E. World Health Organization Laboratory Biosafety
Manual, 2nd edition. WHO Albany, NY ORDER FROM: WHO Publication Centre,
USA, (Q Corp) 49 Sheridan Avenue, Albany, New York 12210; Phone: (518)
436-9686 (Order # 1152213) (cost $23.40 plus $3.00 handling).
Appendix B-VI-F. A U.S. Department of Agriculture permit, required
for import and interstate transport of pathogens, may be obtained from
the U.S. Department of Agriculture, ATTN: Animal and Plant Health
Inspection Service, Import-Export Products Office, Room 756, Federal
Building, 6505 Belcrest Road, Hyattsville, Maryland 20782. Telephone;
301-436-7830 or 8499; FAX 301-436-8226
Appendix B-VI-G. National Cancer Institute Safety Standards for
Research Involving Oncogenic Viruses, October 1974. U.S. Department of
Health, Education, and Welfare (Publication # (NIH) 75-790).
Appendix B-VI-H. All activities, including storage of variola and
whitepox, are restricted to the single national facility (World Health
Organization Collaborating Center for Smallpox Research, Centers for
Disease Control and Prevention, Atlanta, Georgia).
Appendix B-VI-I. Published regulations or guidelines from Federal,
State, or local governments must also be taken into account.
Appendix B-VI-J. U.S. Department of Labor, Occupational Safety and
Health Administration. 1991. Occupational Exposure to Bloodborne
Pathogens, Final Rule (56 FR 64175-64182).
The rest of the NIH Guidelines will have terminology changes (i.e.,
Class 1, 2, 3, 4 will be changed to Risk Group 1, 2, 3, 4,
respectively. Class 5 will become restrictive pathogens.) Cross
references will be changed accordingly to revision in Appendix B.
XV. Report From Ad Hoc Review Committee
On March 8 and May 1, 1995, the Ad hoc Review Committee met to
discuss three major topics for review: (1) domain and mandate of the
Recombinant DNA Advisory Committee; (2) composition of the Recombinant
DNA Advisory Committee; and (3) Recombinant DNA Advisory Committee's
review of human gene transfer protocols. Dr. Nelson Wivel will give a
status report on the Ad hoc Review Committee.
XVI. Presentation on Fetal Sheep Studies/Zanjani
Dr. Esmail Zanjani of the Veterans Administration Hospital Medical
Center, Reno, Nevada, will be giving a presentation on Fetal Sheep
Studies. Dr. Zanjani will present results of his experimental work on
in utero cell transfer.
OMB's ``Mandatory Information Requirements for Federal Assistance
Program Announcements'' (45 FR 39592, June 11, 1980) requires a
statement concerning the official government programs contained in the
Catalog of Federal Domestic Assistance. Normally, NIH lists in its
announcements the number and title of affected individual programs for
the guidance of the public. Because the guidance in this notice covers
not only virtually every NIH program but also essentially every Federal
research program in which DNA recombinant molecule techniques could be
used, it has been determined not to be cost effective or in the public
interest to attempt to list these programs. Such a list would likely
require several additional pages. In addition, NIH could not be certain
that every Federal program would be included as many Federal agencies,
as well as private organizations, both national and international, have
elected to follow the NIH Guidelines. In lieu of the individual program
listing, NIH invites readers to direct questions to the information
address above about whether individual programs listed in the Catalog
of Federal Domestic Assistance are affected.
Effective Date: May 9, 1995.
Daryl A. Chamblee,
Acting Deputy Director for Science Policy and Technology Transfer.
[FR Doc. 95-12405 Filed 5-19-95; 8:45 am]
BILLING CODE 4140-01-P
