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DEPARTMENT OF HEALTH AND of etiological agents described in the experiment by the Institutional HUMAN SERVICES Biosafety in Microbiological and Biosafety Committees and the Biomedical Laboratories, 3rd edition, investigators. Since the new Appendix National Institutes of Health May 1993, U.S. Department of Health B is primarily concerned with human and Human Services, should be pathogenicity, it addresses only the Recombinant DNA Research: Actions endorsed by the Committee. The human etiologic agents and omits all Under the Guidelines Committee retained the option to adopt animal agents. The Committee observed AGENCY: National Institutes of Health, any modifications to the Centers for that this omission created a problem PHS, DHHS. Disease Control and Prevention listing. because some of the animal agents, ACTION: Notice of Actions under the NIH The Committee recommended that the particularly the group of viruses known Guidelines for Research Involving revised Appendix B, Classification of as oncogenic viruses are frequently used Recombinant DNA Molecules (59 FR Microorganisms on the Basis of Hazard, as vectors for gene transfer in the 34496, 59 FR 40170, 60 FR 20726). submitted by Dr. Fleming should not be laboratories or in human studies. The adopted until the Committee received Recombinant DNA Advisory Committee SUMMARY: This notice sets forth an letters of concurrence from both the approved a motion to: (1) establish a action to be taken by the Director, Centers for Disease Control and working group to recommend National Institutes of Health (NIH), Prevention and the NIH Division of exemption of additional vector systems under the NIH Guidelines for Research Safety. in Appendix C (exempt host-vector Involving Recombinant DNA Molecules. In a telephone call on October 20, systems), and (2) accept the proposed FOR FURTHER INFORMATION CONTACT: 1994, Dr. Fleming stated that Appendix amendments to Appendix B with the Additional information can be obtained B, Classification of Microorganisms on provision to develop a new Appendix from Dr. Nelson A. Wivel, Director, the Basis of Hazard, would be reviewed B–V relating to animal viruses relevant Office of Recombinant DNA Activities by experts from the Centers for Disease to human studies, and to list specific (ORDA), Office of Science Policy and Control and Prevention and the examples of agents under Appendix B– Technology Transfer, National Institutes American Society for Microbiology. The I, Risk Group 1 (RG1) Agents. The of Health, Suite 302, 6000 Executive revised Appendix B was submitted to motion was approved by a vote of 17 in Boulevard, MSC 7010, Bethesda, the Recombinant DNA Advisory favor, 0 opposed, and no abstentions. Maryland 20892–7010, (301) 496–9838. Committee December 1–2, 1994, On June 13, 1995, the Office of SUPPLEMENTARY INFORMATION: Today’s meeting for review and discussion. Recombinant DNA Activities forwarded action is being promulgated under the During the December 1994 meeting, the two versions of the Appendix B–V, NIH Guidelines for Research Involving Committee recommended publishing Animal Viral Etiologic Agents in Recombinant DNA Molecules. This the revised Appendix B in the Federal Common Use to the Appendix B proposed action was published for Register for public comment, with Subcommittee. Most of these agents comment in the Federal Register of further review of this proposal and were previously listed as Class 2 August 18, 1994 (58 FR 44098), possible approval during the March 6– oncogenic viruses in two separate November 8, 1994 (59 FR 55796), 7, 1995, meeting. categories of low and moderate risk During the March 6–7, 1995 meeting, February 8, 1995 (60 FR 7630), and May agents in the original Appendix B. Since the Recombinant DNA Advisory 22, 1995 (60 FR 27207), and reviewed none of these animal etiologic agents are Committee deferred approval of the associated with disease in healthy and recommended for approval by the proposed amendments to Appendix B human adults, one version of Appendix NIH Recombinant DNA Advisory pending additional revisions to the B–V listed these agents as a single group Committee (RAC) at its meeting on June remaining sections and appendices of recommended for Biosafety Level 1 8–9, 1995. the NIH Guidelines that are required to containment and another version listed I. Background Information and adequately accommodate the revised them in a two-tier system for either Decisions on Actions Under the NIH Appendix B (Sections II, III, IV, V, Biosafety Level 1 or Biosafety Level 2 Guidelines Appendices C, H, and Q). The motion containment. Subsequent discussion for deferral included a recommendation with the members of the Appendix B A. Amendments to Sections II, III, IV, V, that a subcommittee consisting of Dr. Subcommittee concluded that while Appendices B, C, H, and Q of the NIH Stephen Straus (Chair of the there was no reason to have a separate Guidelines Regarding Updating the Subcommittee), ad hoc experts, and group of ‘‘moderate’’ risk agents in this Classification of Microorganisms Office of Recombinant DNA Activities list, it was prudent to recommend In a letter dated June 24, 1993, Dr. staff would meet to develop the required conducting experiments under a Diane Fleming, President of the Mid- modifications. The motion passed by a Biosafety Level 2 containment with Atlantic Biological Safety Association vote of 17 in favor, 0 opposed, and no several agents that are capable of requested the revision and updating of abstentions. infecting human cells, e.g., amphotropic Appendix B, Classification of On May 5, 1995, the Appendix B and xenotropic murine leukemia virus. Microorganisms on the Basis of Hazard. Subcommittee met to finalize the During the September 11–12, 1995, The Mid-Atlantic Biological Safety document in terms of its listing of meeting, the Recombinant DNA Association submitted an updated list of pathogens and the text of the NIH Advisory Committee reviewed the the classification of microorganisms for Guidelines related to Appendix B in updated Appendix B along with other the Recombinant DNA Advisory other sections and appendices (Sections sections and appendices of the NIH Committee to review which included II, III, IV, V, Appendices C, H, and Q). Guidelines (Sections II, III, IV, V, the latest taxonomy and agent risk group During the June 8–9, 1995 meeting, the Appendices C, H, and Q) relating to classifications as defined by the Centers Recombinant DNA Advisory Committee classification of microorganisms. It was for Disease Control and Prevention. reviewed the document. There was a observed that some viruses in the During the September 9–10, 1993, concurrence that the Risk Group moderate risk group could infect human meeting, the Recombinant DNA classification serves as an initial cells but their replication was largely Advisory Committee recommended by guidance to assign an appropriate restricted to their animal hosts. Some consensus that the current classification containment level for a particular Committee members pointed out that Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices 1483 some viruses with oncogenes such as therapeutic interventions may be biosafety containment level for SV40 have been treated more cautiously available. (4) Risk Group 4 (RG4) agents recombinant DNA experiments than viruses without oncogenes; are likely to cause serious or lethal described in Sections III–A, therefore, a two-tier list should be used. human disease for which preventive or Experiments that Require Institutional Dr. Wivel explained that listing a group therapeutic interventions are not Biosafety Committee Approval, RAC of animal viruses as ‘‘moderate risk’’ usually available. Review, and NIH Director Approval agents introduces an inconsistency into Section II–A–2. Criteria for Risk Groups Before Initiation, III–B, Experiments that Appendix B. Some strains of these Require NIH/ORDA and Institutional viruses, although capable of infecting Classification of agents is based on the Biosafety Committee Approval Before human cells, have not been shown to be potential effect of a biological agent on Initiation, and III–C, Experiments that associated with any disease in healthy a healthy human adult and does not Require Institutional Biosafety human adults. They fall within the account for instances in which an Committee Approval Before Initiation. definition of Risk Group 1 agents, i.e., individual may have increased Careful consideration should be given agents that are not associated with susceptibility to such agents, e.g., to the types of manipulation planned for disease in healthy adult humans. Two preexisting diseases, medications, some higher Risk Group agents. For committee members inquired why compromised immunity, pregnancy or example, the RG2 dengue viruses may several viruses in the original Appendix breast feeding (which may increase be cultured under the Biosafety Level B are not listed in the new version. Dr. exposure of infants to some agents) (see (BL) 2 containment (see Section II–B); Thomas Shih (Executive Secretary, Appendix B, Classification of Human however, when such agents are used for Appendix B Subcommittee) explained Etiologic Agents on the Basis of Hazard). animal inoculation or transmission Personnel may need periodic medical that several rarely used viruses such as studies, a higher containment level is surveillance to ascertain fitness to chick embryo lethal orphan virus are recommended. Similarly, RG3 agents perform certain activities; they may also deleted from the new list. The list such as Venezuelan equine need to be offered prophylactic vaccines includes commonly used organisms, encephalomyelitis and yellow fever and boosters (see Section IV–B–1–f, and it is not intended to be inclusive Responsibilities of the Institution, viruses should be handled at a higher since many other animal agents are not General Information). containment level for animal listed. Dr. Walters (Chair, Recombinant inoculation and transmission DNA Advisory Committee) stated that Section II–A–3. Comprehensive Risk experiments. the consensus of the committee is to Assessment Individuals working with human accept the list of animal viruses in In deciding on the appropriate immunodeficiency virus (HIV), hepatitis Appendix B–V as a reasonable containment for an experiment, the B virus (HBV) or other bloodborne modification of Appendix B. initial risk assessment from Appendix pathogens should consult Occupational The actions are detailed in Section B, Classification of Human Etiologic Exposure to Bloodborne Pathogens; II—Summary of Actions. I accept these Agents on the Basis of Hazard, should Final Rule (56 FR 64175–64182). BL2 recommendations, and the NIH be followed by a thorough consideration containment is recommended for Guidelines will be amended of the agent itself and how it is to be activities involving all blood- accordingly. manipulated. Factors to be considered contaminated clinical specimens, body II. Summary of Actions in determining the level of containment fluids, and tissues from all humans, or include agent factors such as: virulence, from HIV- or HBV-infected or A. Amendments to Section II, Safety pathogenicity, infectious dose, inoculated laboratory animals. Considerations (Previously the Entire environmental stability, route of spread, Activities such as the production of Section II was Entitled Containment) communicability, operations, quantity, research-laboratory scale quantities of Section II is amended to read: availability of vaccine or treatment, and HIV or other bloodborne pathogens, gene product effects such as toxicity, manipulating concentrated virus Section II. Safety Considerations physiological activity, and allergenicity. preparations, or conducting procedures Section II–A. Risk Assessment Any strain that is known to be more that may produce droplets or aerosols, are performed in a BL2 facility using the Section II–A–1. Risk Groups hazardous than the parent (wild-type) strain should be considered for handling additional practices and containment Risk assessment requires the exercise at a higher containment level. Certain equipment recommended for BL3. of sound judgment by the investigator. attenuated strains or strains that have Activities involving industrial scale The investigator must make an initial been demonstrated to have irreversibly volumes or preparations of concentrated risk assessment based on the Risk Group lost known virulence factors may HIV are conducted in a BL3 facility, or (RG) of an agent (see Appendix B, qualify for a reduction of the BL3 Large Scale if appropriate, using Classification of Human Etiologic containment level compared to the Risk BL3 practices and containment Agents on the Basis of Hazard). Agents Group assigned to the parent strain (see equipment. are classified into four Risk Groups Section V–B, Footnotes and References Exotic plant pathogens and animal (RGs) according to their relative of Sections I through IV). pathogens of domestic livestock and pathogenicity for healthy adult humans A final assessment of risk based on poultry are restricted and may require by the following criteria: (1) Risk Group these considerations is then used to set special laboratory design, operation and 1 (RG1) agents are not associated with the appropriate containment conditions containment features not addressed in disease in healthy adult humans. (2) for the experiment (see Section II–B, Biosafety in Microbiological and Risk Group 2 (RG2) agents are Containment). The containment level Biomedical Laboratories (see Section V– associated with human disease which is required may be equivalent to the Risk C, Footnotes and References of Sections rarely serious and for which preventive Group classification of the agent or it I through IV). For information regarding or therapeutic interventions are often may be raised or lowered as a result of the importation, possession, or use of available. (3) Risk Group 3 (RG3) agents the above considerations. The these agents see Sections V–G and V–H, are associated with serious or lethal Institutional Biosafety Committee must Footnotes and References of Sections I human disease for which preventive or approve the risk assessment and the through IV. 1484 Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices

Section II–B. Containment whole animals at BL4 or BL4–N with plant or animal pathogens (see Effective biological safety containment. Section V–G, Footnotes and References Section III–C–1–d. Containment programs * * * of Sections I through IV). conditions for experiments involving Section III–C–3. Experiments [Rest of Section II remains unchanged.] the introduction of recombinant DNA Involving the Use of Infectious DNA or B. Amendments to Section III, into restricted agents shall be set on a RNA Viruses or Defective DNA or RNA Experiments Covered by the NIH case-by-case basis following NIH/ORDA Viruses in the Presence of Helper Virus Guidelines review. A U.S. Department of in Tissue Culture Systems. Agriculture permit is required for work Caution: Special care should be used Section III–C is amended to read: with plant or animal pathogens (see in the evaluation of containment levels Section III–C. Experiments That Require Section V–G and V–L, Footnotes and for experiments which are likely to Institutional Biosafety Committee References of Sections I through IV). either enhance the pathogenicity (e.g., Approval Before Initiation Experiments with such agents shall be insertion of a host oncogene) or to conducted with whole animals at BL4 or extend the host range (e.g., introduction Prior to the initiation of an BL4–N containment. of novel control elements) of viral experiment that falls into this category, Section III–C–2. Experiments in vectors under conditions that permit a the Principal Investigator must submit a which DNA From Risk Group 2, Risk productive infection. In such cases, registration document to the Group 3, Risk Group 4, or Restricted serious consideration should be given to Institutional Biosafety Committee which Agents (see Section V–A, Footnotes and increasing physical containment by at contains the following information: (i) References of Sections I through IV) is least one level. the source(s) of DNA; (ii) the nature of Cloned into Nonpathogenic Prokaryotic Note: Recombinant DNA or RNA the inserted DNA sequences; (iii) the or Lower Eukaryotic Host-Vector molecules derived therefrom, which host(s) and vector(s) to be used; (iv) an Systems. contain less than two-thirds of the indication of what protein will be Section III–C–2–a. Experiments in genome of any eukaryotic virus (all produced if an attempt is to be made to which DNA from Risk Group 2 or Risk viruses from a single Family) (See obtain expression of a foreign gene; and Group 3 agents (see Section II–A, Risk Section V–J, Footnotes and References (v) the containment conditions that will Assessment) is transferred into of Sections I through IV) being be implemented as specified in the NIH nonpathogenic prokaryotes or lower considered identical (see Section V–K, Guidelines. For experiments in this eukaryotes may be performed under BL2 Footnotes and References of Sections I category, the registration document containment. Experiments in which through IV), are considered defective shall be dated, signed by the Principal DNA from Risk Group 4 agents is and may be used in the absence of Investigator, and filed with the transferred into nonpathogenic helper virus under the conditions Institutional Biosafety Committee. The prokaryotes or lower eukaryotes may be specified in Section III–D–1, Institutional Biosafety Committee shall performed under BL2 containment after Experiments Involving the Formation of review and approve all experiments in demonstration that only a totally and Recombinant DNA Molecules this category prior to their initiation. irreversibly defective fraction of the Containing No More than Two-Thirds of Requests to decrease the level of agent’s genome is present in a given the Genome of any Eukaryotic Virus. containment specified for experiments recombinant. In the absence of such a Section III–C–3–a. Experiments in this category will be considered by demonstration, BL4 containment shall involving the use of infectious or NIH (see Section IV–C–1–b–(2)–(c), be used. The Institutional Biosafety defective Risk Group 2 viruses (see Minor Actions). Committee may approve the specific Section V–A, Footnotes and References Section III–C–1. Experiments Using lowering of containment for particular of Sections I through IV, and Appendix Risk Group 2, Risk Group 3, Risk Group experiments to BL1. Many experiments B–II, Risk Group 2 Agents) in the 4, or Restricted Agents as Host-Vector in this category are exempt from the presence of helper virus may be Systems (see Section II–A, Risk NIH Guidelines (see Section III–E, conducted at BL2. Assessment). Exempt Experiments). Experiments Section III–C–3–b. Experiments Section III–C–1–a. Experiments involving the formation of recombinant involving the use of infectious or involving the introduction of DNA for certain genes coding for defective Risk Group 3 viruses (see recombinant DNA into Risk Group 2 molecules toxic for vertebrates require Section V–A, Footnotes and References agents will usually be conducted at NIH/ORDA approval (see Section III–B– of Sections I through IV, and Appendix Biosafety Level (BL) 2 containment. 1, Experiments Involving the Cloning of B–III–D, Risk Group 3 (RG3)—Viruses Experiments with such agents will Toxin Molecules With LD50 of Less than and Prions) in the presence of helper usually be conducted with whole 100 Nanograms Per Kilogram Body virus may be conducted at BL3. animals at BL2 or BL2–N (Animals) Weight) or shall be conducted under Section III–C–3–c. Experiments containment. NIH specified conditions as described in involving the use of infectious or Section III–C–1–b. Experiments Appendix F, Containment Conditions defective Risk Group 4 viruses (see involving the introduction of for Cloning of Genes Coding for the Section V–A, Footnotes and References recombinant DNA into Risk Group 3 Biosynthesis of Molecules Toxic for of Sections I through IV, and Appendix agents will usually be conducted at BL3 Vertebrates. B–IV–D, Risk Group 4 (RG4)—Viral containment. Experiments with such Section III–C–2–b. Containment Agents) in the presence of helper virus agents will usually be conducted with conditions for experiments in which may be conducted at BL4. whole animals at BL3 or BL3–N DNA from restricted agents is Section III–C–3–d. Experiments containment. transferred into nonpathogenic involving the use of infectious or Section III–C–1–c. Experiments prokaryotes or lower eukaryotes shall be defective restricted poxviruses (see involving the introduction of determined by NIH/ORDA following a Section V–A and V–L, Footnotes and recombinant DNA into Risk Group 4 case-by-case review (see Section V–L, References of Sections I through IV) in agents shall be conducted at BL4 Footnotes and References of Sections I the presence of helper virus shall be containment. Experiments with such through IV). A U.S. Department of determined on a case-by-case basis agents will usually be conducted with Agriculture permit is required for work following NIH/ORDA review. A U.S. Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices 1485

Department of Agriculture permit is References of Sections I through IV. It is c–(1), Principal Investigator). For cases required for work with plant or animal important that the investigator falling under Sections III–A through III– pathogens (see Section V–G, Footnotes demonstrate that the fraction of the viral D, Experiments Covered by the NIH and References of Sections I through genome being utilized does not lead to Guidelines, this judgment is to be IV). productive infections. A U.S. reviewed and approved by the Section III–C–3–e. Experiments Department of Agriculture permit is Institutional Biosafety Committee as involving the use of infectious or required for work with plant or animal part of its responsibility to make an defective viruses in the presence of pathogens (see Section V–G, Footnotes ‘‘independent assessment of the helper virus which are not covered in and References of Sections I through containment levels required by the NIH Sections III–E–3–a through III–C–3–d IV). Guidelines for the proposed research’’ may be conducted at BL1. Section III–C–4–b. For experiments (see Section IV–B–2–b–(1), Institutional Section III–C–4. Experiments involving recombinant DNA, or DNA or Biosafety Committee). The Institutional Involving Whole Animals. RNA derived therefrom, involving Biosafety Committee may refer specific This section covers experiments whole animals, including transgenic cases to NIH/ORDA as part of NIH/ involving whole animals in which the animals, and not covered by Sections ORDA’s functions to ‘‘provide advice to animal’s genome has been altered by III–C–1, Experiments Using Risk Group all within and outside NIH’’ (see Section stable introduction of recombinant 2, Risk Group 3, Risk Group 4, or IV–C–3, Office of Recombinant DNA DNA, or DNA derived therefrom, into Restricted Agents as Host-Vector Activities). NIH/ORDA may request the germ-like (transgenic animals) and Systems, or III–C–4–a, Experiments advice from the RAC as part of the experiments involving viable Involving Whole Animals, the RAC’s responsibility for ‘‘interpreting recombinant DNA-modified appropriate containment shall be the NIH Guidelines for experiments to microorganisms tested on whole determined by the Institutional which the NIH Guidelines do not animals. For the latter, other than Biosafety Committee. specifically assign containment levels’’ viruses which are only vertically [The rest of the Section III–C remains (see Section IV–C–1–b–(2)–(f), Minor transmitted, the experiments may not be unchanged.] Actions). conducted at BL1–N containment. A Section V–C. U.S. Department of minimum containment of BL2 or BL2– C. Amendments to Section IV, Roles and Health and Human Services, Public N is required. Responsibilities Health Service, Centers for Disease Caution—Special care should be used Section IV–C–1–b–(2)–(e) is amended Control and Prevention and the National in the evaluation of containment to read: Institutes of Health. Biosafety in conditions for some experiments with Section IV–C–1–b–(2)–(e). Setting Microbiological and Biomedical transgenic animals. For example, such containment under Sections III–C–1–d, Laboratories, 3rd edition, 1993. Copies experiments might lead to the creation Experiments Using Risk Group 2, Risk are available from: Superintendent of of novel mechanisms or increased Group 3, Risk Group 4, or Restricted Documents, U.S. Government Printing transmission of a recombinant pathogen Agents as Host-Vector Systems, and III– Office, Washington, DC 20402 (stock or production of undesirable traits in C–2–b, Experiments in which DNA from # 017–040–00523–7), Phone (202)–512– the host animal. In such cases, serious Risk Group 2, Risk Group 3, Risk Group 2356. consideration should be given to 4, or Restricted Agents is Cloned into Section V–D. Classification of increasing the containment conditions. Nonpathogenic Prokaryotic or Lower Etiologic Agents on the Basis of Hazard, Section III–C–4–a. Recombinant DNA, Eukaryotic Host-Vector Systems; 4th Edition, July 1974, U.S. Department or DNA or RNA molecules derived [The rest of the Section IV–C–1–b–(2) of Health, Education, and Welfare, therefrom, from any source except for remains unchanged.] Public Health Service, Centers for greater than two-thirds of eukaryotic Disease Control, Office of Biosafety, viral genome may be transferred to any D. Amendments to Section V, Footnotes Atlanta, Georgia 30333. nonhuman vertebrate or any and References of Sections I Through IV Section V–E. Benenson, Abram S. ed., invertebrate organism and propagated Section V is amended to read: Control of Communicable Diseases in under conditions of physical Man, 15th edition. 1990. American containment comparable to BL1 or BL1– Section V. Footnotes and References of Public Health Association, Washington, N and appropriate to the organism Sections I through IV DC. under study (see Section V–B, Footnotes Section V–A. The NIH Director, with Section V–F. World Health and References of Sections I through advice of the RAC, may revise the Organization Laboratory Biosafety IV). Animals that contain sequences classification for the purposes of the Manual, 2nd edition. 1993. WHO from viral vectors, which do not lead to NIH Guidelines (see Section IV–C–1–b– Albany, NY. Copies are available from: transmissible infection either directly or (2)–(e), Minor Actions). The revised list WHO Publication Centre, USA, (Q Corp) indirectly as a result of of organisms in each risk group is 49 Sheridan Avenue, Albany, New York complementation or recombination in reprinted in Appendix B, Classification 12210; Phone: (518)–436–9686 (Order animals, may be propagated under of Human Etiologic Agents on the Basis # 1152213). conditions of physical containment of Hazard. Section V–G. A U.S. Department of comparable to BL1 or BL1–N and Section V–B. Section III, Experiments Agriculture permit, required for import appropriate to the organism under Covered by the NIH Guidelines, and interstate transport of plant and study. Experiments involving the describes a number of places where animal pathogens, may be obtained from introduction of other sequences from judgments are to be made. In all these the U.S. Department of Agriculture, eukaryotic viral genomes into animals cases, the Principal Investigator shall ATTN: Animal and Plant Health are covered under Section III–C–4–b, make the judgment on these matters as Inspection Service (APHIS), Veterinary Experiments Involving Whole Animals. part of his/her responsibility to ‘‘make Services, National Center for Import- For experiments involving recombinant the initial determination of the required Export, Products Program, 4700 River DNA-modified Risk Groups, 2, 3, 4, or levels of physical and biological Road, Unit 40, Riverdale, MD 20737. restricted organisms, see Sections V–A, containment in accordance with the Phone: (301)–734–8499; Fax: (301)–734– V–G, and V–L, Footnotes and NIH Guidelines’’ (see Section IV–B–4– 8226. 1486 Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices

Section V–H. American Type Culture considered. Non-infectious life cycle Bacillus subtilis or Bacillus Collection Catalogues of plant viruses, stages of parasites are excluded. licheniformis Host-Vector Systems, animal viruses, cells, bacteria, fungi, etc. This appendix reflects the current Exceptions), Eschenrichia coli-K12 (see are available from American Type state of knowledge and should be Appendix C–II–A, Escherichia coli K–12 Culture Collection, 12301 Parklawn considered a resource document. The Host-Vector Systems, Exceptions), and Drive, Rockville, Maryland 20852–1776. more commonly encountered agents are adeno-associated virus types 1–4. Phone: (800)–638–6597; Fax: (301)–231– included; however, this appendix is not Those agents not listed in Risk Groups 5826. meant to be all inclusive. Information (RGs) 2, 3 and 4 are not automatically Section V–I. U.S. Department of on agent risk assessment may be found or implicitly classified in RG1; a risk Labor, Occupational Safety and Health in the Agent Summary Statements of the assessment must be conducted based on Administration. 1991. Occupational Centers for Disease Control and the known and potential properties of Exposure to Bloodborne Pathogens, Prevention/National Institutes of Health the agents and their relationship to Final Rule (56 FR 64175–64182). publications, Biosafety in agents that are listed. Section V–J. As classified in the 6th Microbiological and Biomedical Laboratories (see Sections V–C, V–D, V– Appendix B–II. Risk Group 2 (RG2) Report on the International Committee Agents on Taxonomy of Viruses: Classification E, and V–F, Footnotes and References of and Nomenclature of Viruses, F.A. Sections I through IV). Further guidance RG2 agents are associated with human Murphy et al., Archives of Virology/ on agents not listed in Appendix B may disease which is rarely serious and for Supplement 10, 1995, Springer-Verlag, be obtained through: Centers for Disease which preventive or therapeutic New York, New York. Control and Prevention, Biosafety interventions are often available. Branch, Atlanta, Georgia 30333, Phone: Section V–K. i.e., the total of all (404)–639–3883, Fax: (404)–639–2294; Appendix B–II–A. Risk Group 2 (RG2)— genomes within a family shall not National Institutes of Health, Division of Bacterial Agents Including Chlamydia exceed two-thirds of the genome. Safety, Bethesda, Maryland 20892, —Acinetobacter baumannii (formerly Section V–L. Organisms including Phone: (301)–496–1357; National Acinetobacter calcoaceticus) alastrim, smallpox (variola) and Animal Disease Center, U.S. Department —Actinobacillus whitepox may not be studied in the of Agriculture, Ames, Iowa 50010, —Actinomyces pyogenes (formerly United States except at specified Phone: (515)–862–8258. Corynebacterium pyogenes) facilities. All activities, including A special committee of the American —Aeromonas hydrophila storage of variola and whitepox, are Society for Microbiology will conduct —Amycolata autotrophica restricted to the single national facility an annual review of this appendix and —Archanobacterium haemolyticum (World Health Organization its recommendation for changes will be (formerly Corynebacterium Collaborating Center for Smallpox presented to the Recombinant DNA haemolyticum) Research, Centers for Disease Control Advisory Committee as proposed —Arizona hinshawii—all serotypes and Prevention, Atlanta, Georgia). amendments to the NIH Guidelines. —Bacillus anthracis Section V–M. In accordance with —Bartonella henselae, B. quintana, B. accepted scientific and regulatory Appendix B—Table 1.—Basis for the Classification of Biohazardous Agents by vinsonii practices of the discipline of plant —Bordetella including B. pertussis pathology, an exotic plant pathogen Risk Group (RG) Risk Group 1 Agents that are not associ- —Borrelia recurrentis, B. burgdorferi (e.g., virus, bacteria, or fungus) is one —Burkholderia (formerly Pseudomonas that is unknown to occur within the (RG1). ated with disease in healthy adult humans. species) except those listed in U.S. (see Section V–G, Footnotes and Risk Group 2 Agents that are associated Appendix B–III–A (RG3)) References of Sections I through IV). (RG2). with human disease —Campylobacter coli, C. fetus, C. jejuni Determination of whether a pathogen which is rarely serious —Chlamydia psittaci, C. trachomatis, C. has a potential for serious detrimental and for which preventive pneumoniae impact on managed (agricultural, forest, or therapeutic interven- —Clostridium botulinum, Cl. chauvoei, grassland) or natural ecosystems should tions are often available. Cl. haemolyticum, Cl. histolyticum, be made by the Principal Investigator Risk Group 3 Agents that are associated Cl. novyi, Cl. septicum, Cl. tetani and the Institutional Biosafety (RG3). with serious or lethal dis- ease for which preventive —Corynebacterium diphtheriae, C. Committee, in consultation with or therapeutic interven- pseudotuberculosis, C. renale scientists knowledgeable of plant tions may be available —Dermatophilus congolensis diseases, crops, and ecosystems in the (high individual risk but —Edwardsiella tarda geographic area of the research. low community risk). —Erysipelothrix rhusiopathiae Risk Group 4 Agents that are likely to E. Amendments to Appendix B, —Escherichia coli—all (RG4). cause serious or lethal enteropathogenic, enterotoxigenic, Classification of Human Etiologic human disease for which Agents on the Basis of Hazard enteroinvasive and strains bearing K1 preventive or therapeutic antigen, including E. coli O157:H7 Appendix B is amended to read: interventions are not usu- —Haemophilus ducreyi, H. influenzae ally available (high indi- Appendix B. Classification of Human vidual risk and high com- —Helicobacter pylori Etiologic Agents on the Basis of Hazard munity risk). —Klebsiella—all species except K. oxytoca (RG1) Appendix B includes those biological Appendix B–I. Risk Group 1 (RG1) —Legionella including L. pneumophila agents known to infect humans, as well Agents —Leptospira interrogans—all serotypes as selected animal agents, that may pose RG1 agents are not associated with —Listeria theoretical risks if inoculated into disease in healthy adult humans. —Moraxella humans. Included in the lists are Examples of RG1 agents include —Mycobacterium (except those listed in species known to be pathogenic, asporogenic Bacillus subtilis or Bacillus Appendix B–III–A (RG3)) including mutated, or recombined; non- licheniformis (see Appendix C–IV–A, M. avium complex, M. asiaticum, M. pathogenic species and strains are not bovis BCG vaccine strain, M. chelonei, Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices 1487

M. fortuitum, M. kansasii, M. leprae, —Heterophyes —Other viruses as listed in the reference M. malmoense, M. marinum, M. —Hymenolepis including H. diminuta, source (see Section V–C, Footnotes paratuberculosis, M. scrofulaceum, M. H. nana and References of Sections I through simiae, M. szulgai, M. ulcerans, M. —Isospora IV) xenopi —Leishmania including L. braziliensis, Hepatitis A, B, C, D, and E Viruses —Mycoplasma, except M. mycoides and L. donovani, L. ethiopia, L. major, L. M. agalactiae which are restricted mexicana, L. peruvania, L. tropica —Herpesviruses—except Herpesvirus animal pathogens —Loa loa filaria worms simiae (Monkey B virus) (see —Neisseria gonorrhoea, N. meningitidis —Microsporidium Appendix B–IV–D, Risk Group 4 —Nocardia asteroides, N. brasiliensis, —Naegleria fowleri (RG4)—Viral Agents) N. otitidiscaviarum, N. transvalensis —Necator human hookworms including —Cytomegalovirus —Rhodococcus equi N. americanus —Epstein Barr virus —Salmonella including S. arizonae, S. —Onchoerca filaria worms including, —Herpes simplex types 1 and 2 cholerasuis, S. enteritidis, S. —Herpes zoster O. volvulus —Human herpesvirus types 6 and 7 gallinarum-pullorum, S. meleagridis, —Plasmodium including simian S. paratyphi, A, B, C, S. typhi, S. species, P. cynomologi, P. falciparum, Orthomyxoviruses typhimurium P. malariae, P. ovale, P. vivax —Influenza viruses types A, B, and C —Shigella including S. boydii, S. —Sarcocystis including S. sui hominis —Other tick-borne orthomyxoviruses as dysenteriae, type 1, S. flexneri, S. —Schistosoma including S. listed in the reference source (see sonnei haematobium, S. intercalatum, S. Section V–C, Footnotes and —Sphaerophorus necrophorus japonicum, S. mansoni, S. mekongi References of Sections I through IV) —Staphylococcus aureus —Strongyloides including S. stercoralis —Streptobacillus moniliformis —Taenia solium Papovaviruses —Streptococcus including S. —Toxocara including T. canis —All human papilloma viruses pneumoniae, S. pyogenes —Toxoplasma including T. gondii Paramyxoviruses —Treponema pallidum, T. carateum —Trichinella spiralis —Vibrio cholerae, V. parahemolyticus, —Trypanosoma including T. brucei —Newcastle disease virus V. vulnificus brucei, T. brucie gambiense, T. brucei —Measles virus —Yersinia enterocolitica rhodesiense, T. cruzi —Mumps virus —Wuchereria bancrofti filaria worms —Parainfluenza viruses types 1, 2, 3, Appendix B–II–B. Risk Group 2 (RG2)— and 4 Fungal Agents Appendix B–II–D. Risk Group 2 (RG2)— —Respiratory syncytial virus Viruses —Blastomyces dematitidis Parvoviruses —Cladosporium bantianum, C. Adenoviruses, Human—All Types (xylohypha) trichoides —Human parvovirus (B19) Alphaviruses (Togaviruses)—Group A —Cryptococcus neofomans Picornaviruses —Dactylaria galopava (Ochroconis Arboviruses gallopavum) —Coxsackie viruses types A and B —Eastern equine encephalomyelitis —Echoviruses—all types —Epidermophyton virus —Polioviruses—all types, wild and —Exophiala (Wangiella) dermatitidis —Venezuelan equine encephalomyelitis attenuated —Fonsecaea pedrosoi vaccine strain TC–83 —Rhinoviruses—all types —Microsporum —Western equine encephalomyelitis —Poxviruses—all types except —Paracoccidioides braziliensis virus Monkeypox virus (see Appendix B– —Penicillium marneffei Arenaviruses III–D, Risk Group 3 (RG3)—Viruses —Sporothrix schenckii and Prions) and restricted poxviruses —Trichophyton —Lymphocytic choriomeningitis virus including Alastrim, Smallpox, and Appendix B–II–C. Risk Group 2 (RG2)— (non-neurotropic strains) White-pox (see Section V–L, Parasitic Agents —Tacaribe virus complex Footnotes and References of Sections —Other viruses as listed in the reference I through IV) —Ancylostoma human hookworms source (see Section V–C, Footnotes —Reoviruses—all types including including A. duodenale, A. and References of Sections I through Coltivirus, human Rotavirus, and ceylanicum IV) Orbivirus (Colorado tick fever virus) —Ascaris including Ascaris lumbricoides suum Bunyaviruses Rhabdoviruses —Babesia including B. divergens, B. —Bunyamwera virus —Rabies virus—all strains microti —Rift Valley fever virus vaccine strain —Vesicular stomatitis virus—laboratory —Brugia filaria worms including B. MP–12 adapted strains including VSV- malayi, B. timori —Other viruses as listed in the reference Indiana, San Juan, and Glasgow —Coccidia source (see Section V–C, Footnotes Togaviruses (see Alphaviruses and —Cryptosporidium including C. parvum and References of Sections I through Flaviviruses) —Cysticercus cellulosae (hydatid cyst, IV) larva of T. solium) —Rubivirus (rubella) —Echinococcus including E. granulosis, Calciviruses Appendix B–III. Risk Group 3 (RG3) E. multilocularis, E. vogeli Coronaviruses —Entamoeba histolytica Agents —Enterobius Flaviviruses (Togaviruses)—Group B RG3 agents are associated with —Fasciola including F. gigantica, F. Arboviruses serious or lethal human disease for hepatica —Dengue virus serotypes 1, 2, 3, and 4 which preventive or therapeutic —Giardia including G. lamblia —Yellow fever virus vaccine strain 17D interventions may be available. 1488 Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices

Appendix B–III–A. Risk Group 3 Prions Appendix B–V. Animal Viral Etiologic (RG3)—Bacterial Agents Including —Transmissible spongioform Agents in Common Use Rickettsia encephalopathies (TME) agents The following list of animal etiologic —Bartonella (Creutzfeldt-Jakob disease and kuru agents is appended to the list of human —Brucella including B. abortus, B. agents) (for containment instruction, etiologic agents. None of these agents is canis, B. suis see Section V–C, Footnotes and associated with disease in healthy adult —Burkholderia (Pseudomonas) mallei, References of Sections I through IV) humans; They are commonly used in laboratory experimental work. B. pseudomallei Retroviruses —Coxiella burnetii A containment level appropriate for —Francisella tularensis —Human immunodeficiency virus RG1 human agents is recommended for —Mycobacterium bovis (except BCG (HIV) types 1 and 2 their use. For agents that are infectious strain, see Appendix B–II–A, Risk —Human T cell lymphotropic virus to human cells, e.g., amphotropic and Group 2 (RG2)—Bacterial Agents (HTLV) types 1 and 2 xenotropic strains of murine leukemia Including Chlamydia); M. —Simian immunodeficiency virus (SIV) virus, a containment level appropriate tuberculosis Rhabdoviruses for RG2 human agents is recommended. —Pasteurella multocida type B— —Vesicular stomatitis virus Baculoviruses ‘‘buffalo’’ and other virulent strains —Rickettsia akari, R. australis, R. Appendix B–IV. Risk Group 4 (RG4) Herpesviruses canada, R. conorii, R. prowazekii, R. Agents —Herpesvirus ateles rickettsii, R. siberica, R. RG4 agents are likely to cause serious —Herpesvirus saimiri tsutsugamushi, R. typhi (R. mooseri) or lethal human disease for which —Marek’s disease virus —Yersinia pestis preventive or therapeutic interventions —Murine cytomegalovirus Appendix B–III–B. Risk Group 3 are not usually available. Papovaviruses (RG3)—Fungal Agents Appendix B–IV–A. Risk Group 4 —Bovine papilloma virus —Coccidioides immitis (sporulating (RG4)—Bacterial Agents —Polyoma virus cultures; contaminated soil) None —Shope papilloma virus —Histoplasma capsulatum, H. —Simian virus 40 (SV40) capsulatum var. duboisii Appendix B–IV–B. Risk Group 4 (RG4)—Fungal Agents Retroviruses Appendix B–III–C. Risk Group 3 —Avian leukosis virus (RG3)—Parasitic Agents None —Avian sarcoma virus None Appendix B–IV–C. Risk Group 4 —Bovine leukemia virus (RG4)—Parasitic Agents Appendix B–III–D. Risk Group 3 —Feline leukemia virus (RG3)—Viruses and Prions None —Feline sarcoma virus —Gibbon leukemia virus Appendix B–IV–D. Risk Group 4 Alphaviruses (Togaviruses)—Group A —Mason-Pfizer monkey virus (RG4)—Viral Agents Arboviruses —Mouse mammary tumor virus —Semliki Forest virus Arenaviruses (Togaviruses)—Group A —Murine leukemia virus —St. Louis encephalitis virus Arboviruses —Murine sarcoma virus —Venezuelan equine encephalomyelitis —Guanarito virus —Rat leukemia virus virus (except the vaccine strain TC– —Lassa virus F. Amendments to Appendix C, 83, see Appendix B–II–D, Risk Group —Junin virus Exemptions Under Section III–E–6 2 (RG2)—Viruses) —Machupo virus —Other viruses as listed in the reference Appendix C–I–A is amended to read: Bunyaviruses (Nairovirus) source (see Section V–C, Footnotes Appendix C–I–A. Exceptions and References of Sections I through —Crimean-Congo hemorrhagic fever IV) virus The following categories are not exempt from the NIH Guidelines: (i) Arenaviruses Filoviruses experiments described in Section III–A —Lymphocytic choriomeningitis virus —Ebola virus which require Institutional Biosafety (LCM) (neurotropic strains) —Marburg virus Committee approval, RAC review, and NIH Director approval before initiation, Bunyaviruses Flaviruses (Togaviruses)—Group B (ii) experiments described in Section Arboviruses —Hantaviruses including Hantaan virus III–B which require NIH/ORDA and —Rift Valley fever virus —Tick-borne encephalitis virus Institutional Biosafety Committee complex including Absetterov, approval before initiation, (iii) Flaviviruses (Togaviruses)—Group B Central European encephalitis, experiments involving DNA from Risk Arboviruses Hanzalova, Hypr, Kumlinge, Kyasanur Groups 3, 4, or restricted organisms (see —Japanese encephalitis virus Forest disease, Omsk hemorrhagic Appendix B, Classification of Human —Yellow fever virus fever, and Russian spring-summer Etiologic Agents on the Basis of Hazard, —Other viruses as listed in the reference encephalitis viruses and Sections V–G and V–L, Footnotes and References of Sections I through IV) source (see Section V–C, Footnotes Herpesviruses (alpha) and References of Sections I through or cells known to be infected with these IV) —Herpesvirus simiae (Herpes B or agents, (iv) experiments involving the Monkey B virus) deliberate introduction of genes coding Poxviruses Hemorrhagic fever agents and viruses for the biosynthesis of molecules that —Monkeypox virus as yet undefined. are toxic for vertebrates (see Appendix Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices 1489

F, Containment Conditions for Cloning containment conditions specified in experiments involving DNA from Risk of Genes Coding for the Biosynthesis of Section III–C–2, Experiments in which Groups 3, 4, or restricted organisms (see Molecules Toxic for Vertebrates), and DNA from Risk Group 2, Risk Group 3, Appendix B, Classification of Human (v) whole plants regenerated from plant Risk Group 4, or Restricted Agents is Etiologic Agents on the Basis of Hazard, cells and tissue cultures are covered by Cloned into Nonpathogenic Prokaryotic and Sections V–G and V–L, Footnotes the exemption provided they remain or Lower Eukaryotic Host-Vector and References of Sections I through IV) axenic cultures even though they Systems, with prior Institutional or cells known to be infected with these differentiate into embryonic tissue and Biosafety Committee review and agents, may be conducted under regenerate into plantlets. approval, (iv) large scale experiments containment conditions specified in Appendix C–II–A is amended to read: (e.g., more than 10 liters of culture), and Section III–C–2, Experiments in which Appendix C–II–A. Exceptions (v) experiments involving the deliberate DNA from Risk Group 2, Risk Group 3, cloning of genes coding for the Risk Group 4, or Restricted Agents is The following categories are not biosynthesis of molecules toxic for Cloned into Nonpathogenic Prokaryotic exempt from the NIH Guidelines: (i) vertebrates (see Appendix F, or Lower Eukaryotic Host-Vector experiments described in Section III–A Containment Conditions for Cloning of Systems, with prior Institutional which require Institutional Biosafety Genes Coding for the Biosynthesis of Biosafety Committee review and Committee approval, RAC review, and Molecules Toxic for Vertebrates). approval, (iv) large scale experiments NIH Director approval before initiation, Appendix C–IV–A is amended to (e.g., more than 10 liters of culture), and (ii) experiments described in Section read: (v) experiments involving the deliberate III–B which require NIH/ORDA and Appendix C–IV–A. Exceptions cloning of genes coding for the Institutional Biosafety Committee biosynthesis of molecules toxic for approval before initiation, (iii) The following categories are not vertebrates (see Appendix F, experiments involving DNA from Risk exempt from the NIH Guidelines: (i) Containment Conditions for Cloning of Groups 3, 4, or restricted organisms (see experiments described in Section III–A Genes Coding for the Biosynthesis of Appendix B, Classification of Human which require Institutional Biosafety Molecules Toxic for Vertebrates). Etiologic Agents on the Basis of Hazard, Committee approval, RAC review, and Appendix C–VI is amended to read: and Sections V–G and V–L, Footnotes NIH Director approval before initiation, and References of Sections I through IV) (ii) experiments described in Section Appendix C–VI. Footnotes and or cells known to be infected with these III–B which require NIH/ORDA and References of Appendix C agents, may be conducted under Institutional Biosafety Committee Appencix C–VI–A. The NIH Director, containment conditions specified in approval before initiation, (iii) with advice of the RAC, may revise the Section III–C–2, Experiments in which experiments involving DNA from Risk Appendix B classification for the DNA from Risk Group 2, Risk Group 3, Groups 3, 4, or restricted organisms (see purposes of these NIH Guidelines (see Risk Group 4, or Restricted Agents is Appendix B, Classification of Human Section IV–C–1–b–(2)–(b), NIH Director- Cloned into Nonpathogenic Prokaryotic Etiologic Agents on the Basis of Hazard, Specific Responsibilities). The revised or Lower Eukaryotic Host-Vector and Sections V–G and V–L, Footnotes list of organisms in each Risk Group is Systems, with prior Institutional and References of Sections I through IV) reprinted in Appendix B. Biosafety Committee review and or cells known to be infected with these approval, (iv) large scale experiments agents, may be conducted under G. Amendments to Appendix H, (e.g., more than 10 liters of culture), and containment conditions specified in Shipment (v) experiments involving the cloning of Section III–C–2, Experiments in which Appendix H–III is amended to read: toxin molecule genes coding for the DNA from Risk Group 2, Risk Group 3, biosynthesis of molecules toxic for Risk Group 4, or Restricted Agents is Appendix H–III. Footnotes and vertebrates (see Appendix F, Cloned into Nonpathogenic Prokaryotic References of Appendix H Containment Conditions for Cloning of or Lower Eukaryotic Host-Vector For further information on shipping Genes Coding for the Biosynthesis of Systems, with prior Institutional etiologic agents contact: (i) The Centers Molecules Toxic for Vertebrates). Biosafety Committee review and for Disease Control and Prevention, Appendix C–III–A is amended to approval, (iv) large scale experiments ATTN: Biohazards Control Office, 1600 read: (e.g., more than 10 liters of culture), and Clifton Road, Atlanta, Georgia 30333, (404) 639–3883, FTS 236–3883; (ii) The Appendix C–III–A. Exceptions (v) experiments involving the deliberate cloning of genes coding for the U.S. Department of Transportation, The following categories are not biosynthesis of molecules toxic for ATTN: Office of Hazardous Materials exempt from the NIH Guidelines: (i) vertebrates (see Appendix F, Transportation, 400 7th Street SW., experiments described in Section III–A Containment Conditions for Cloning of Washington, DC 20590, (202) 366–4545; which require Institutional Biosafety Genes Coding for the Biosynthesis of or (iii) U.S. Department of Agriculture, Committee approval, RAC review, and Molecules Toxic for Vertebrates). ATTN: Animal and Plant Health NIH Director approval before initiation, Appendix C–V–A is amended to read: Inspection Service (APHIS), Veterinary (ii) experiments described in Section Services, National Center for Import- Appendix C–V–A. Exceptions III–B which require NIH/ORDA and Export, Products Program, 4700 River Institutional Biosafety Committee The following categories are not Road, Unit 40, Riverdale, MD 20737. approval before initiation, (iii) exempt from the NIH Guidelines: (i) Phone: (301) 734–8499; Fax: (301) 734– experiments involving DNA from Risk experiments described in Section III–A 8226. Groups 3, 4, or restricted organisms (see which require Institutional Biosafety Appendix B, Classification of Human Committee approval, RAC review, and H. Amendments to Appendix Q, Etiologic Agents on the Basis of Hazard, NIH Director approval before initiation, Physical and Biological Containment for and Sections V–G and V–L, Footnotes (ii) experiments described in Section Recombinant DNA Research Involving and References of Sections I through IV) III–B which require NIH/ORDA and Animals or cells known to be infected with these Institutional Biosafety Committee Appendix Q–III–C is amended to agents, may be conducted under approval before initiation, (iii) read: 1490 Federal Register / Vol. 61, No. 13 / Friday, January 19, 1996 / Notices

Appendix Q–III–C. Risk Group 4 and scientists who are trained and essentially every Federal research restricted microorganisms (see experienced in working with these program in which DNA recombinant Appendix B, Classification of Human agents and in the special containment molecule techniques could be used, it Etiologic Agents on the Basis of Hazard, facilities. has been determined not to be cost and Sections V–G and V–L, Footnotes Within work areas of the animal effective or in the public interest to and References of Sections I through IV) facility, all activities shall be confined attempt to list these programs. Such a pose a high level of individual risk for to the specially equipped animal rooms list would likely require several acquiring life-threatening diseases to or support areas. The maximum animal additional pages. In addition, NIH could containment area and support areas personnel and/or animals. To import not be certain that every Federal shall have special engineering and animal or plant pathogens, special program would be included as many design features to prevent the approval must be obtained from U.S. Federal agencies, as well as private Department of Agriculture, Animal and dissemination of microorganisms into the environment via exhaust air or organizations, both national and Plant Health Inspection Service international, have elected to follow the (APHIS), Veterinary Services, National waste disposal. OMB’s ‘‘Mandatory Information NIH Guidelines. In lieu of the Center for Import-Export, Products Requirements for Federal Assistance individual program listing, NIH invites Program, 4700 River Road, Unit 40, Program Announcements’’ (45 FR readers to direct questions to the Riverdale, MD 20737. Phone: (301) 734– 39592, June 11, 1980) requires a information address above about 8499; Fax: (301) 734–8226. statement concerning the official whether individual programs listed in Laboratory staff shall be required to government programs contained in the the Catalog of Federal Domestic have specific and thorough training in Catalog of Federal Domestic Assistance. Assistance are affected. handling extremely hazardous Normally, NIH lists in its Effective Date: December 14, 1995. infectious agents, primary and announcements the number and title of secondary containment, standard and affected individual programs for the Harold Varmus, special practices, and laboratory design guidance of the public. Because the Director, National Institutes of Health. characteristics. The laboratory staff shall guidance in this notice covers not only [FR Doc. 96–689 Filed 1–18–96; 8:45 am] be supervised by knowledgeable virtually every NIH program but also BILLING CODE 4140±01±M