[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/<greek-b>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)           
----------------------------------------------------------------------------------------------------------------
                                                Examples of                                                     
  Risk group (RG)      Biosafety level         laboratories        Laboratory practices      Safety equipment   
----------------------------------------------------------------------------------------------------------------
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).                                     
----------------------------------------------------------------------------------------------------------------

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]
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