Section III-E.            Experiments that Require Institutional Biosafety Committee Notice Simultaneous with Initiation

Experiments not included in Sections III-A, III-B, III-C, III-D, III-F, and their subsections are considered in Section III-E.  All such experiments may be conducted at BL1 containment.  For experiments in this category, a registration document (see Section III-D, Experiments that Require Institutional Biosafety Committee Approval Before Initiation) shall be dated and signed by the investigator and filed with the local Institutional Biosafety Committee at the time the experiment is initiated.  The Institutional Biosafety Committee reviews and approves all such proposals, but Institutional Biosafety Committee review and approval prior to initiation of the experiment is not required (see Section IV-A, Policy).  For example, experiments in which all components derived from non-pathogenic prokaryotes and non-pathogenic lower eukaryotes fall under Section III-E and may be conducted at BL1 containment.

Section III-E-1.                         Experiments Involving the Formation of Recombinant DNA Molecules Containing No More than Two-Thirds of the Genome of any Eukaryotic Virus

Recombinant DNA molecules containing no more than two-thirds of the genome of any eukaryotic virus (all viruses from a single Family being considered identical [see Section V-J, Footnotes and References of Sections I-IV]) may be propagated and maintained in cells in tissue culture using BL1 containment.  For such experiments, it must be demonstrated that the cells lack helper virus for the specific Families of defective viruses being used.  If helper virus is present, procedures specified under Section III-D-3, Experiments Involving the Use of Infectious Animal or Plant DNA or RNA Viruses or Defective Animal or Plant DNA or RNA Viruses in the Presence of Helper Virus in Tissue Culture Systems, should be used.  The DNA may contain fragments of the genome of viruses from more than one Family but each fragment shall be less than two-thirds of a genome.

Section III-E-2.                        Experiments Involving Whole Plants

This section covers experiments involving recombinant DNA-modified whole plants, and/or experiments involving recombinant DNA-modified organisms associated with whole plants, except those that fall under Section III-A, III-B, III-D, or III-F.  It should be emphasized that knowledge of the organisms and judgment based on accepted scientific practices should be used in all cases in selecting the appropriate level of containment.  For example, if the genetic modification has the objective of increasing pathogenicity or converting a non-pathogenic organism into a pathogen, then a higher level of containment may be appropriate depending on the organism, its mode of dissemination, and its target organisms.  By contrast, a lower level of containment may be appropriate for small animals associated with many types of recombinant DNA-modified plants.

Section III-E-2-a.  BL1-P is recommended for all experiments with recombinant DNA-containing plants and plant-associated microorganisms not covered in Section III-E-2-b or other sections of the NIH Guidelines.  Examples of such experiments are those involving recombinant DNA-modified plants that are not noxious weeds or that cannot interbreed with noxious weeds in the immediate geographic area, and experiments involving whole plants and recombinant DNA-modified non-exotic (see Section V-M, Footnotes and References of Sections I-IV) microorganisms that have no recognized potential for rapid and widespread dissemination or for serious detrimental impact on managed or natural ecosystems (e.g., Rhizobium spp. and Agrobacterium spp.).

Section III-E-2-b.  BL2-P or BL1-P + biological containment is recommended for the following experiments:

Section III-E-2-b-(1).  Plants modified by recombinant DNA that are noxious weeds or can interbreed with noxious weeds in the immediate geographic area.

Section III-E-2-b-(2).  Plants in which the introduced DNA represents the complete genome of a non-exotic infectious agent (see Section V-M, Footnotes and References of Sections I-IV).

Section III-E-2-b-(3).  Plants associated with recombinant DNA-modified non-exotic microorganisms that have a recognized potential for serious detrimental impact on managed or natural ecosystems (see Section V-M, Footnotes and References of Sections I-IV).

Section III-E-2-b-(4).  Plants associated with recombinant DNA-modified exotic microorganisms that have no recognized potential for serious detrimental impact on managed or natural ecosystems (see Section V-M, Footnotes and References of Sections I-IV).

Section III-E-2-b-(5).  Experiments with recombinant DNA-modified arthropods or small animals associated with plants, or with arthropods or small animals with recombinant DNA-modified microorganisms associated with them if the recombinant DNA-modified microorganisms have no recognized potential for serious detrimental impact on managed or natural ecosystems (see Section V-M, Footnotes and References of Sections I-IV).

Section III-E-3.                        Experiments Involving Transgenic Rodents

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

Section III-E-3-a.  Experiments involving the breeding of certain BL1 transgenic rodents are exempt under Section III-F, Exempt Experiments (See Appendix C-VII, Generation of BL1 Transgenic Rodents via Breeding).

Section III-F.            Exempt Experiments

The following recombinant DNA molecules are exempt from the NIH Guidelines and registration with the Institutional Biosafety Committee is not required:

Section III-F-1.  Those that are not in organisms or viruses.

Section III-F-2.  Those that consist entirely of DNA segments from a single nonchromosomal or viral DNA source, though one or more of the segments may be a synthetic equivalent.

Section III-F-3.  Those that consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses when propagated only in that host (or a closely related strain of the same species), or when transferred to another host by well established physiological means.

Section III-F-4.  Those that consist entirely of DNA from an eukaryotic host including its chloroplasts, mitochondria, or plasmids (but excluding viruses) when propagated only in that host (or a closely related strain of the same species).

Section III-F-5.  Those that consist entirely of DNA segments from different species that exchange DNA by known physiological processes, though one or more of the segments may be a synthetic equivalent.  A list of such exchangers will be prepared and periodically revised by the NIH Director with advice of the RAC after appropriate notice and opportunity for public comment (see Section IV-C-1-b-(1)-(c), Major Actions).  See Appendices A-I through A-VI, Exemptions Under Section III-F-5--Sublists of Natural Exchangers, for a list of natural exchangers that are exempt from the NIH Guidelines. 

Section III-F-6.  Those that do not present a significant risk to health or the environment (see Section IV-C-1-b-(1)-(c), Major Actions), as determined by the NIH Director, with the advice of the RAC, and following appropriate notice and opportunity for public comment.  See Appendix C, Exemptions under Section III-F-6 for other classes of experiments which are exempt from the NIH Guidelines.  

SECTION IV.            ROLES AND RESPONSIBILITIES

Section IV-A.            Policy

The safe conduct of experiments involving recombinant DNA depends on the individual conducting such activities.  The NIH Guidelines cannot anticipate every possible situation.  Motivation and good judgment are the key essentials to protection of health and the environment.  The NIH Guidelines are intended to assist the institution, Institutional Biosafety Committee, Biological Safety Officer, and the Principal Investigator in determining safeguards that should be implemented.  The NIH Guidelines will never be complete or final since all conceivable experiments involving recombinant DNA cannot be foreseen.  Therefore, it is the responsibility of the institution and those associated with it to adhere to the intent of the NIH Guidelines as well as to their specifics.  Each institution (and the Institutional Biosafety Committee acting on its behalf) is responsible for ensuring that all recombinant DNA research conducted at or sponsored by that institution is conducted in compliance with the NIH Guidelines.  General recognition of institutional authority and responsibility properly establishes accountability for safe conduct of the research at the local level.  The following roles and responsibilities constitute an administrative framework in which safety is an essential and integral part of research involving recombinant DNA molecules.  Further clarifications and interpretations of roles and responsibilities will be issued by NIH as necessary.

Section IV-B.            Responsibilities of the Institution

Section IV-B-1.                        General Information

Each institution conducting or sponsoring recombinant DNA research which is covered by the NIH Guidelines is responsible for ensuring that the research is conducted in full conformity with the provisions of the NIH Guidelines.  In order to fulfill this responsibility, the institution shall:

Section IV-B-1-a.  Establish and implement policies that provide for the safe conduct of recombinant DNA research and that ensure compliance with the NIH Guidelines.  As part of its general responsibilities for implementing the NIH Guidelines, the institution may establish additional procedures, as deemed necessary, to govern the institution and its components in the discharge of its responsibilities under the NIH Guidelines.  Such procedures may include:  (i) statements formulated by the institution for the general implementation of the NIH Guidelines, and (ii) any additional precautionary steps the institution deems appropriate.

Section IV-B-1-b.  Establish an Institutional Biosafety Committee that meets the requirements set forth in Section IV-B-2-a and carries out the functions detailed in Section IV-B-2-b.

Section IV-B-1-c.  Appoint a Biological Safety Officer (who is also a member of the Institutional Biosafety Committee) if the institution:  (i) conducts recombinant DNA research at Biosafety Level (BL) 3 or BL4, or (ii) engages in large-scale (greater than 10 liters) research.  The Biological Safety Officer carries out the duties specified in Section IV-B-3.

Section IV-B-1-d.  Appoint at least one individual with expertise in plant, plant pathogen, or plant pest containment principles (who is a member of the Institutional Biosafety Committee) if the institution conducts recombinant DNA research that requires Institutional Biosafety Committee approval in accordance with Appendix P, Physical and Biological Containment for Recombinant DNA Research Involving Plants.

Section IV-B-1-e.  Appoint at least one individual with expertise in animal containment principles (who is a member of the Institutional Biosafety Committee) if the institution conducts recombinant DNA research that requires Institutional Biosafety Committee approval in accordance with Appendix Q, Physical and Biological Containment for Recombinant DNA Research Involving Animals.

Section IV-B-1-f.  Ensure that when the institution participates in or sponsors recombinant DNA research involving human subjects:  (i) the Institutional Biosafety Committee has adequate expertise and training (using ad hoc consultants as deemed necessary), (ii) all aspects of Appendix M have been appropriately addressed by the Principal Investigator; and (iii) no research participant shall be enrolled (see definition of enrollment in Section I-E-7) in a human gene transfer experiment until the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements), Institutional Biosafety Committee approval has been obtained,

Institutional Review Board approval has been obtained, and all applicable regulatory authorizations have been obtained.  Institutional Biosafety Committee approval must be obtained from each institution at which recombinant DNA material will be administered to human subjects (as opposed to each institution involved in the production of vectors for human application and each institution at which there is ex vivo transduction of recombinant DNA material into target cells for human application).

Section IV-B-1-g.  Assist and ensure compliance with the NIH Guidelines by Principal Investigators conducting research at the institution as specified in Section IV-B-7.

Section IV-B-1-h.  Ensure appropriate training for the Institutional Biosafety Committee Chair and members, Biological Safety Officer and other containment experts (when applicable), Principal Investigators, and laboratory staff regarding laboratory safety and implementation of the NIH Guidelines.  The Institutional Biosafety Committee Chair is responsible for ensuring that Institutional Biosafety Committee members are appropriately trained.  The Principal Investigator is responsible for ensuring that laboratory staff are appropriately trained.  The institution is responsible for ensuring that the Principal Investigator has sufficient training; however, this responsibility may be delegated to the Institutional Biosafety Committee.

Section IV-B-1-i.  Determine the necessity for health surveillance of personnel involved in connection with individual recombinant DNA projects; and if appropriate, conduct a health surveillance program for such projects.  The institution shall establish and maintain a health surveillance program for personnel engaged in large-scale research or production activities involving viable organisms containing recombinant DNA molecules which require BL3 containment at the laboratory scale.  The institution shall establish and maintain a health surveillance program for personnel engaged in animal research involving viable recombinant DNA-containing microorganisms that require BL3 or greater containment in the laboratory.  The Laboratory Safety Monograph discusses various components of such a program (e.g., records of agents handled, active investigation of relevant illnesses, and the maintenance of serial serum samples for monitoring serologic changes that may result from the employees' work experience).  Certain medical conditions may place a laboratory worker at increased risk in any endeavor where infectious agents are handled.  Examples cited in the Laboratory Safety Monograph include gastrointestinal disorders and treatment with steroids, immunosuppressive drugs, or antibiotics.  Workers with such disorders or treatment should be evaluated to determine whether they should be engaged in research with potentially hazardous organisms during their treatment or illness.  Copies of the Laboratory Safety Monograph are available from the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).

Section IV-B-1-j.  Report any significant problems, violations of the NIH Guidelines, or any significant research-related accidents and illnesses to NIH/OBA within thirty days, unless the institution determines that a report has already been filed by the Principal Investigator or Institutional Biosafety Committee.  Reports shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).

Section IV-B-2.                        Institutional Biosafety Committee (IBC)

The institution shall establish an Institutional Biosafety Committee whose responsibilities need not be restricted to recombinant DNA.  The Institutional Biosafety Committee shall meet the following requirements:

Section IV-B-2-a.                        Membership and Procedures

Section IV-B-2-a-(1).  The Institutional Biosafety Committee must be comprised of no fewer than five members so selected that they collectively have experience and expertise in recombinant DNA technology and the capability to assess the safety of recombinant DNA research and to identify any potential risk to public health or the environment.  At least two members shall not be affiliated with the institution (apart from their membership on the Institutional Biosafety Committee) and who represent the interest of the surrounding community with respect to health and protection of the environment (e.g., officials of state or local public health or environmental protection agencies, members of other local governmental bodies, or persons active in medical, occupational health, or environmental concerns in the community).  The Institutional Biosafety Committee shall include at least one individual with expertise in plant, plant pathogen, or plant pest containment principles when experiments utilizing Appendix P, Physical and Biological Containment for Recombinant DNA Research Involving Plants, require prior approval by the Institutional Biosafety Committee.  The Institutional Biosafety Committee shall include at least one scientist with expertise in animal containment principles when experiments utilizing Appendix Q, Physical and Biological Containment for Recombinant DNA Research Involving Animals, require Institutional Biosafety Committee prior approval.  When the institution conducts recombinant DNA research at BL3, BL4, or Large Scale (greater than 10 liters), a Biological Safety Officer is mandatory and shall be a member of the Institutional Biosafety Committee (see Section IV-B-3, Biological Safety Officer).  When the institution participates in or sponsors recombinant DNA research involving human research participants, the institution must ensure that:  (i) the Institutional Biosafety Committee has adequate expertise and training (using ad hoc consultants as deemed necessary); (ii) all aspects of Appendix M have been appropriately addressed by the Principal Investigator; (iii) no research participant shall be enrolled (see definition of enrollment in Section I-E-7) in a human gene transfer experiment until the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements); and (iv) final IBC approval is granted only after the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements).  Institutional Biosafety Committee approval must be obtained from the institution at which recombinant DNA material will be administered to human research participants (rather than the site involved in manufacturing gene transfer products).

Note:  Individuals, corporations, and institutions not otherwise covered by the NIH Guidelines, are encouraged to adhere to the standards and procedures set forth in Sections I through IV (see Section IV-D, Voluntary Compliance.  The policy and procedures for establishing an Institutional Biosafety Committee under Voluntary Compliance, are specified in Section IV-D-2, Institutional Biosafety Committee Approval).

Section IV-B-2-a-(2).  In order to ensure the competence necessary to review and approve recombinant DNA activities, it is recommended that the Institutional Biosafety Committee:  (i) include persons with expertise in recombinant DNA technology, biological safety, and physical containment; (ii) include or have available as consultants persons knowledgeable in institutional commitments and policies, applicable law, standards of professional conduct and practice, community attitudes, and the environment, and (iii) include at least one member representing the laboratory technical staff.

Section IV-B-2-a-(3).  The institution shall file an annual report with NIH/OBA which includes:  (i) a roster of all Institutional Biosafety Committee members clearly indicating the Chair, contact person, Biological Safety Officer (if applicable), plant expert (if applicable), animal expert (if applicable), human gene therapy expertise or ad hoc consultant(if applicable); and (ii) biographical sketches of all Institutional Biosafety Committee members (including community members).

Section IV-B-2-a-(4).  No member of an Institutional Biosafety Committee may be involved (except to provide information requested by the Institutional Biosafety Committee) in the review or approval of a project in which he/she has been or expects to be engaged or has a direct financial interest.

Section IV-B-2-a-(5).  The institution, that is ultimately responsible for the effectiveness of the Institutional Biosafety Committee, may establish procedures that the Institutional Biosafety Committee shall follow in its initial and continuing review and approval of applications, proposals, and activities.

Section IV-B-2-a-(6).  When possible and consistent with protection of privacy and proprietary interests, the institution is encouraged to open its Institutional Biosafety Committee meetings to the public.

Section IV-B-2-a-(7).  Upon request, the institution shall make available to the public all Institutional Biosafety Committee meeting minutes and any documents submitted to or received from funding agencies which the latter are required to make available to the public.  If public comments are made on Institutional Biosafety Committee actions, the institution shall forward both the public comments and the Institutional Biosafety Committee's response to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).

Section IV-B-2-b.                        Functions

On behalf of the institution, the Institutional Biosafety Committee is responsible for:

Section IV-B-2-b-(1).  Reviewing recombinant DNA research conducted at or sponsored by the institution for compliance with the NIH Guidelines as specified in Section III, Experiments Covered by the NIH Guidelines, and approving those research projects that are found to conform with the NIH Guidelines.  This review shall include:  (i) independent assessment of the containment levels required by the NIH Guidelines for the proposed research; (ii) assessment of the facilities, procedures, practices, and training and expertise of personnel involved in recombinant DNA research; (iii) ensuring that all aspects of Appendix M have been appropriately addressed by the Principal Investigator; (iv) ensuring that no research participant is enrolled (see definition of enrollment in Section I-E-7) in a human gene transfer experiment until the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements), Institutional Biosafety Committee approval (from the clinical trial site) has been obtained, Institutional Review Board approval has been obtained, and all applicable regulatory authorizations have been obtained; (v) for human gene transfer protocols selected for public RAC review and discussion, consideration of the issues raised and recommendations made as a result of this review and consideration of the Principal Investigator’s response to the RAC recommendations; (vi) ensuring that final IBC approval is granted only after the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements); and (vii) ensuring compliance with all surveillance, data reporting, and adverse event reporting requirements set forth in the NIH Guidelines.

Section IV-B-2-b-(2).  Notifying the Principal Investigator of the results of the Institutional Biosafety Committee's review and approval.

Section IV-B-2-b-(3).  Lowering containment levels for certain experiments as specified in Section III-D-2-a, Experiments in which DNA from Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Eukaryotic Host-Vector Systems.

Section IV-B-2-b-(4).  Setting containment levels as specified in Sections III-D-4-b, Experiments Involving Whole Animals, and III-D-5, Experiments Involving Whole Plants.

Section IV-B-2-b-(5).  Periodically reviewing recombinant DNA research conducted at the institution to ensure compliance with the NIH Guidelines.

Section IV-B-2-b-(6).  Adopting emergency plans covering accidental spills and personnel contamination resulting from recombinant DNA research.

Note:  The Laboratory Safety Monograph describes basic elements for developing specific procedures dealing with major spills of potentially hazardous materials in the laboratory, including information and references about decontamination and emergency plans.  The NIH and the Centers for Disease Control and Prevention are available to provide consultation and direct assistance, if necessary, as posted in the Laboratory Safety Monograph.  The institution shall cooperate with the state and local public health departments by reporting any significant research-related illness or accident that may be hazardous to the public health.

Section IV-B-2-b-(7).  Reporting any significant problems with or violations of the NIH Guidelines and any significant research-related accidents or illnesses to the appropriate institutional official and NIH/OBA within 30 days, unless the Institutional Biosafety Committee determines that a report has already been filed by the Principal Investigator.  Reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).

Section IV-B-2-b-(8).  The Institutional Biosafety Committee may not authorize initiation of experiments which are not explicitly covered by the NIH Guidelines until NIH (with the advice of the RAC when required) establishes the containment requirement.

Section IV-B-2-b-(9).  Performing such other functions as may be delegated to the Institutional Biosafety Committee under Section IV-B-2, Institutional Biosafety Committee.

Section IV-B-3.                        Biological Safety Officer (BSO)

Section IV-B-3-a.  The institution shall appoint a Biological Safety Officer if it engages in large-scale research or production activities involving viable organisms containing recombinant DNA molecules.

Section IV-B-3-b.  The institution shall appoint a Biological Safety Officer if it engages in recombinant DNA research at BL3 or BL4.  The Biological Safety Officer shall be a member of the Institutional Biosafety Committee. 

Section IV-B-3-c.  The Biological Safety Officer's duties include, but are not be limited to:

Section IV-B-3-c-(1).  Periodic inspections to ensure that laboratory standards are rigorously followed;

Section IV-B-3-c-(2).  Reporting to the Institutional Biosafety Committee and the institution any significant problems, violations of the NIH Guidelines, and any significant research-related accidents or illnesses of which the Biological Safety Officer becomes aware unless the Biological Safety Officer determines that a report has already been filed by the Principal Investigator;

Section IV-B-3-c-(3).  Developing emergency plans for handling accidental spills and personnel contamination and investigating laboratory accidents involving recombinant DNA research;

Section IV-B-3-c-(4).  Providing advice on laboratory security;

Section IV-B-3-c-(5).  Providing technical advice to Principal Investigators and the Institutional Biosafety Committee on research safety procedures.

Note:  See the Laboratory Safety Monograph for additional information on the duties of the Biological Safety Officer.

Section IV-B-4.                        Plant, Plant Pathogen, or Plant Pest Containment Expert

When the institution conducts recombinant DNA research that requires Institutional Biosafety Committee approval in accordance with Appendix P, Physical and Biological Containment for Recombinant DNA Research Involving Plants, the institution shall appoint at least one individual with expertise in plant, plant pathogen, or plant pest containment principles (who is a member of the Institutional Biosafety Committee).

Section IV-B-5.                        Animal Containment Expert

When the institution conducts recombinant DNA research that requires Institutional Biosafety Committee approval in accordance with Appendix Q, Physical and Biological Containment for Recombinant DNA Research Involving Animals, the institution shall appoint at least one individual with expertise in animal containment principles (who is a member of the Institutional Biosafety Committee).

Section IV-B-6.                        Human Gene Therapy Expertise

When the institution participates in or sponsors recombinant DNA research involving human subjects, the institution must ensure that:  (i) the Institutional Biosafety Committee has adequate expertise and training (using ad hoc consultants as deemed necessary) and (ii) all aspects of Appendix M, Points to Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA Molecules into One or More Human Subjects (Points to Consider) , have been appropriately addressed by the Principal Investigator prior to submission to NIH/OBA. 

Section IV-B-7.                        Principal Investigator (PI)

On behalf of the institution, the Principal Investigator is responsible for full compliance with the NIH Guidelines in the conduct of recombinant DNA research.  A Principal Investigator engaged in human gene transfer research may delegate to another party, such as a corporate sponsor, the reporting functions set forth in Appendix M, with written notification to the NIH OBA of the delegation and of the name(s), address, telephone, and fax numbers of the contact.  The Principal Investigator is responsible for ensuring that the reporting requirements are fulfilled and will be held accountable for any reporting lapses.

Section IV-B-7-a.                        General Responsibilities

As part of this general responsibility, the Principal Investigator shall:

Section IV-B-7-a-(1).  Initiate or modify no recombinant DNA research which requires Institutional Biosafety Committee approval prior to initiation (see Sections III-A, III-B, III-C, III-D, and III-E, Experiments Covered by the NIH Guidelines) until that research or the proposed modification thereof has been approved by the Institutional Biosafety Committee and has met all other requirements of the NIH Guidelines;

Section IV-B-7-a-(2).  Determine whether experiments are covered by Section III-E, Experiments that Require Institutional Biosafety Committee Notice Simultaneous with Initiation, and ensure that the appropriate procedures are followed;

Section IV-B-7-a-(3).  Report any significant problems, violations of the NIH Guidelines, or any significant research-related accidents and illnesses to the Biological Safety Officer (where applicable), Greenhouse/Animal Facility Director (where applicable), Institutional Biosafety Committee, NIH/OBA, and other appropriate authorities (if applicable) within 30 days.  Reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax);

Section IV-B-7-a-(4).  Report any new information bearing on the NIH Guidelines to the Institutional Biosafety Committee and to NIH/OBA (reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax);

Section IV-B-7-a-(5).  Be adequately trained in good microbiological techniques;

Section IV-B-7-a-(6).  Adhere to Institutional Biosafety Committee approved emergency plans for handling accidental spills and personnel contamination; and

Section IV-B-7-a-(7).  Comply with shipping requirements for recombinant DNA molecules (see Appendix H, Shipment, for shipping requirements and the Laboratory Safety Monograph for technical recommendations).

Section IV-B-7-b.                        Information to Be Submitted by the Principal Investigator to NIH OBA

The Principal Investigator shall:

Section IV-B-7-b-(1).  Submit information to NIH/OBA for certification of new host-vector systems;

Section IV-B-7-b-(2).  Petition NIH/OBA, with notice to the Institutional Biosafety Committee, for proposed exemptions to the NIH Guidelines;

Section IV-B-7-b-(3).  Petition NIH/OBA, with concurrence of the Institutional Biosafety Committee, for approval to conduct experiments specified in Sections III-A-1, Major Actions Under the NIH Guidelines, and III-B, Experiments that Require NIH/OBA and Institutional Biosafety Committee Approval Before Initiation;

Section IV-B-7-b-(4).  Petition NIH/OBA for determination of containment for experiments requiring case-by-case review; and

Section IV-B-7-b-(5).  Petition NIH/OBA for determination of containment for experiments not covered by the NIH Guidelines.

Section IV-B-7-b-(6).  Ensure that all aspects of Appendix M have been appropriately addressed prior to submission of a human gene transfer experiment to NIH OBA, and provide a letter signed by the Principal Investigator(s) on institutional letterhead acknowledging that the documentation being submitted to NIH OBA complies with the requirements set forth in Appendix M.  No research participant shall be enrolled (see definition of enrollment in Section I-E-7) in a human gene transfer experiment until the RAC review process has been completed (see Appendix M-I-B, RAC Review Requirements); IBC approval (from the clinical trial site) has been obtained; Institutional Review Board (IRB) approval has been obtained; and all applicable regulatory authorization(s) have been obtained.

For a clinical trial site that is added after the RAC review process, no research participant shall be enrolled (see definition of enrollment in Section I-E-7) at the clinical trial site until the following documentation has been submitted to NIH OBA:  (1) IBC approval (from the clinical trial site); (2) IRB approval; (3) IRB-approved informed consent document; (4) curriculum vitae of the principal investigator(s) (no more than two pages in biographical sketch format); and (5) NIH grant number(s) if applicable.

Section IV-B-7-c.                        Submissions by the Principal Investigator to the Institutional Biosafety Committee

The Principal Investigator shall:

Section IV-B-7-c-(1).  Make an initial determination of the required levels of physical and biological containment in accordance with the NIH Guidelines;

Section IV-B-7-c-(2).  Select appropriate microbiological practices and laboratory techniques to be used for the research;

Section IV-B-7-c-(3).  Submit the initial research protocol and any subsequent changes (e.g., changes in the source of DNA or host-vector system), if covered under Sections III-A, III-B, III-C, III-D, or III-E (Experiments Covered by the NIH Guidelines), to the Institutional Biosafety Committee for review and approval or disapproval; and

Section IV-B-7-c-(4).  Remain in communication with the Institutional Biosafety Committee throughout the conduct of the project.

Section IV-B-7-d.                        Responsibilities of the Principal Investigator Prior to Initiating Research

The Principal Investigator shall:

Section IV-B-7-d-(1).  Make available to all laboratory staff the protocols that describe the potential biohazards and the precautions to be taken;

Section IV-B-7-d-(2).  Instruct and train laboratory staff in:  (i) the practices and techniques required to ensure safety, and (ii) the procedures for dealing with accidents; and

Section IV-B-7-d-(3).  Inform the laboratory staff of the reasons and provisions for any precautionary medical practices advised or requested (e.g., vaccinations or serum collection).

Section IV-B-7-e.                        Responsibilities of the Principal Investigator During the Conduct of the Research

The Principal Investigator shall:

Section IV-B-7-e-(1).  Supervise the safety performance of the laboratory staff to ensure that the required safety practices and techniques are employed;

Section IV-B-7-e-(2).  Investigate and report any significant problems pertaining to the operation and implementation of containment practices and procedures in writing to the Biological Safety Officer (where applicable), Greenhouse/Animal Facility Director (where applicable), Institutional Biosafety Committee, NIH/OBA, and other appropriate authorities (if applicable) (reports to NIH/OBA shall be sent to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax);

Section IV-B-7-e-(3).  Correct work errors and conditions that may result in the release of recombinant DNA materials; and

Section IV-B-7-e-(4).  Ensure the integrity of the physical containment (e.g., biological safety cabinets) and the biological containment (e.g., purity and genotypic and phenotypic characteristics).

Section IV-B-7-e-(5).  Comply with reporting requirements for human gene transfer experiments conducted in compliance with the NIH Guidelines (see Appendix M-I-C, Reporting Requirements).

Section IV-C.                        Responsibilities of the National Institutes of Health (NIH)

Section IV-C-1.                        NIH Director

The NIH Director is responsible for:  (i) establishing the NIH Guidelines, (ii) overseeing their implementation, and (iii) their final interpretation.  The NIH Director has responsibilities under the NIH Guidelines that involve OBA and RAC.  OBA's responsibilities under the NIH Guidelines are administrative.  Advice from RAC is primarily scientific, technical, and ethical.  In certain circumstances, there is specific opportunity for public comment with published response prior to final action.

Section IV-C-1-a.                        General Responsibilities

The NIH Director is responsible for:

Section IV-C-1-a-(1).  Promulgating requirements as necessary to implement the NIH Guidelines;

Section IV-C-1-a-(2).  Establishing and maintaining RAC to carry out the responsibilities set forth in Section IV-C-2, Recombinant DNA Advisory Committee (RAC membership is specified in its charter and in Section IV-C-2);

Section IV-C-1-a-(3).  Establishing and maintaining NIH/OBA to carry out the responsibilities defined in Section IV-C-3, Office of Biotechnology Activities;

Section IV-C-1-a-(4).  Conducting and supporting training programs in laboratory safety for Institutional Biosafety Committee members, Biological Safety Officers and other institutional experts (if applicable), Principal Investigators, and laboratory staff.

Section IV-C-1-a-(5).  Establishing and convening Gene Therapy Policy Conferences as described in Appendix L, Gene Therapy Policy Conferences.

Section IV-C-1-b.                        Specific Responsibilities

In carrying out the responsibilities set forth in this section, the NIH Director, or a designee shall weigh each proposed action through appropriate analysis and consultation to determine whether it complies with the NIH Guidelines and presents no significant risk to health or the environment.

Section IV-C-1-b-(1).    Major Actions

To execute Major Actions, the NIH Director shall seek the advice of RAC and provide an opportunity for public and Federal agency comment.  Specifically, the Notice of Meeting and Proposed Actions shall be published in the Federal Register at least 15 days before the RAC meeting.  The NIH Director's decision/recommendation (at his/her discretion) may be published in the Federal Register for 15 days of comment before final action is taken.  The NIH Director's final decision/recommendation, along with responses to public comments, shall be published in the Federal Register.  The RAC and Institutional Biosafety Committee Chairs shall be notified of the following decisions:

Section IV-C-1-b-(1)-(a).  Changing containment levels for types of experiments that are specified in the NIH Guidelines when a Major Action is involved;

Section IV-C-1-b-(1)-(b).  Assigning containment levels for types of experiments that are not explicitly considered in the NIH Guidelines when a Major Action is involved;

Section IV-C-1-b-(1)-(c).  Promulgating and amending a list of classes of recombinant DNA molecules to be exempt from the NIH Guidelines because they consist entirely of DNA segments from species that exchange DNA by known physiological processes or otherwise do not present a significant risk to health or the environment;

Section IV-C-1-b-(1)-(d).  Permitting experiments specified by Section III-A, Experiments that Require Institutional Biosafety Committee Approval, RAC Review, and NIH Director Approval Before Initiation;

Section IV-C-1-b-(1)-(e).  Certifying new host-vector systems with the exception of minor modifications of already certified systems (the standards and procedures for certification are described in Appendix I-II, Certification of Host-Vector Systems).  Minor modifications constitute (e.g., those of minimal or no consequence to the properties relevant to containment); and

Section IV-C-1-b-(1)-(f).  Adopting other changes in the NIH Guidelines.

Section IV-C-1-b-(2).    Minor Actions

NIH/OBA shall carry out certain functions as delegated to it by the NIH Director (see Section IV-C-3, Office of Biotechnology Activities).  Minor Actions (as determined by NIH/OBA in consultation with the RAC Chair and one or more RAC members, as necessary) will be transmitted to RAC and Institutional Biosafety Committee Chairs:

Section IV-C-1-b-(2)-(a).  Changing containment levels for experiments that are specified in Section III, Experiments Covered by the NIH Guidelines (except when a Major Action is involved);

Section IV-C-1-b-(2)-(b).  Assigning containment levels for experiments not explicitly considered in the NIH Guidelines;

Section IV-C-1-b-(2)-(c).  Revising the Classification of Etiologic Agents for the purpose of these NIH Guidelines (see Section V-A, Footnotes and References of Sections I-IV).

Section IV-C-1-b-(2)-(d).  Interpreting the NIH Guidelines for experiments to which the NIH Guidelines do not specifically assign containment levels;

Section IV-C-1-b-(2)-(e).  Setting containment under Sections III-D-1-d, Experiments Using Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-Vector Systems, and III-D-2-b, Experiments in which DNA from Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Eukaryotic Host-Vector Systems;

Section IV-C-1-b-(2)-(f).  Approving minor modifications of already certified host-vector systems (the standards and procedures for such modifications are described in Appendix I-II, Certification of Host-Vector Systems);

Section IV-C-1-b-(2)-(g).  Decertifying already certified host-vector systems;

Section IV-C-1-b-(2)-(h).  Adding new entries to the list of molecules toxic for vertebrates (see Appendix F, Containment Conditions for Cloning of Genes Coding for the Biosynthesis of Molecules Toxic for Vertebrates); and

Section IV-C-1-b-(2)-(i).  Determining appropriate containment conditions for experiments according to case precedents developed under Section IV-C-1-b-(2)-(c).

Section IV-C-2.                        Recombinant DNA Advisory Committee (RAC)

The RAC is responsible for carrying out the functions specified in the NIH Guidelines, as well as others specified in its charter or assigned by the Secretary of Health and Human Services or the NIH Director.  The RAC membership and procedures, in addition to those set forth in the NIH Guidelines, are specified in the charter for the RAC which is filed as provided in the General Services Administration Federal Advisory Committee Management regulations, 41 CFR part 101-6, and is available on the OBA web site, http://oba.od.nih.gov/oba/rac/RACCharter2009.pdf.  In the event of a conflict between the NIH Guidelines and the charter, the charter shall control.

The RAC will consist of not less than 15 voting members, including the Chair, appointed under the procedures of the NIH and the Department of Health and Human Services.  The maximum number of voting members will be established in the charter of the RAC.  At least a majority of the voting members must be knowledgeable in relevant scientific fields, e.g., molecular genetics, molecular biology, recombinant DNA research, including clinical gene transfer research.  At least 4 members of the RAC must be knowledgeable in fields such as public health, laboratory safety, occupational health, protection of human subjects of research, the environment, ethics, law, public attitudes or related fields.  Representatives of the Federal agencies listed in the charter shall serve as non-voting members.  Nominations for RAC members may be submitted to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).

All meetings of the RAC shall be announced in the Federal Register, including tentative agenda items, 15 days before the meeting.  Final agendas, if modified, shall be available at least 72 hours before the meeting.  No item defined as a Major Action under Section IV-C-1-b-(1) may be added to an agenda following Federal Register publication.

RAC shall be responsible for:

Section IV-C-2-a.  Advising the NIH Director on the following actions:  (1) Adopting changes in the NIH Guidelines.  (2) Assigning containment levels, changing containment levels, and approving experiments considered as Major Actions under the NIH Guidelines, i.e., the deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire the trait naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture.  (3) Promulgating and amending lists of classes of recombinant DNA molecules to be exempt from the NIH Guidelines because they consist entirely of DNA segments from species that exchange DNA by known physiological processes or otherwise do not present a significant risk to health or the environment.  (4) Certifying new host-vector systems.

Section IV-C-2-b.  Identifying novel human gene transfer experiments deserving of public discussion by the full RAC;

Section IV-C-2-c.  Transmitting to the NIH Director specific comments/ recommendations about:  (i) a specific human gene transfer experiment, or (ii) a category of human gene transfer experiments;

Section IV-C-2-d.  Publicly reviewing human gene transfer clinical trial data and relevant information evaluated and summarized by NIH/OBA in accordance with the annual data reporting requirements;

Section IV-C-2-e.  Identifying broad scientific, safety, social, and ethical issues relevant to gene therapy research as potential Gene Therapy Policy Conference topics;

Section IV-C-2-f. Identifying novel social and ethical issues relevant to specific human applications of gene transfer and recommending appropriate modifications to the Points to Consider that will provide guidance in the preparation of relevant Informed Consent documents; and

Section IV-C-2-g.  Identifying novel scientific and safety issues relevant to specific human applications of gene transfer and recommending appropriate modifications to the Points to Consider that will provide guidance in the design and submission of human gene transfer clinical trials.

Section IV-C-3.                        Office of Biotechnology Activities (OBA)

OBA shall serve as a focal point for information on recombinant DNA activities and provide advice to all within and outside NIH including institutions, Biological Safety Officers, Principal Investigators, Federal agencies, state and local governments, and institutions in the private sector.  OBA shall carry out such other functions as may be delegated to it by the NIH Director.  OBA's responsibilities include (but are not limited to) the following:

Section IV-C-3-a.  Serving as the focal point for public access to summary information pertaining to human gene transfer experiments;

Section IV-C-3-b.  Serving as the focal point for data management of human gene transfer experiments;

Section IV-C-3-c.  Administering the annual data reporting requirements (and subsequent review) for human gene transfer experiments (see Appendix M-I-C, Reporting Requirements);

Section IV-C-3-d.  Transmitting comments/recommendations arising from public RAC discussion of a novel human gene transfer experiment to the NIH Director.  RAC recommendations shall be forwarded to the Principal Investigator, the sponsoring institution, and other DHHS components, as appropriate.

Section IV-C-3-e.  Collaborating with Principal Investigators, Institutional Biosafety Committees, Institutional Review Boards, and other DHHS components (including FDA and the Office for Human Research Protections), to ensure human gene transfer experiment registration compliance in accordance with Appendix M-I, Requirements for Protocol Submission, Review, and Reporting-Human Gene Transfer Experiments of the NIH Guidelines.

Section IV-C-3-f.  Administering Gene Therapy Policy Conferences as deemed appropriate by the NIH Director (see Appendix L, Gene Therapy Policy Conferences).

Section IV-C-3-g.  Reviewing and approving experiments in conjunction with ad hoc experts involving the cloning of genes encoding for toxin molecules that are lethal for vertebrates at an LD₅₀ of less than or equal to 100 nanograms per kilogram body weight in organisms other than Escherichia coli K-12 (see Section III-B-1, Experiments Involving the Cloning of Toxin Molecules with LD₅₀ of Less than 100 Nanograms Per Kilogram Body Weight, Appendix F, Containment Conditions for Cloning of Genes Coding for the Biosynthesis of Molecules Toxic for Vertebrates);

Section IV-C-3-h.  Serving as the executive secretary of RAC;

Section IV-C-3-i.  Publishing in the Federal Register:

Section IV-C-3-i-(1).  Announcements of RAC meetings and tentative agendas at least 15 days in advance (Note:  If the agenda for a RAC meeting is modified, OBA shall make the revised agenda available to anyone upon request in advance of the meeting);

Section IV-C-3-i-(2).  Announcements of Gene Therapy Policy Conferences and tentative agendas at least 15 days in advance;

Section IV-C-3-i-(3).  Proposed Major Actions (see Section IV-C-1-b-(1), Major Actions) at least 15 days prior to the RAC meeting; and

Section IV-C-3-j.  Reviewing and approving the membership of an institution's Institutional Biosafety Committee, and where it finds the Institutional Biosafety Committee meets the requirements set forth in Section IV-B-2, Institutional Biosafety Committee (IBC), giving its approval to the Institutional Biosafety Committee membership.

Section IV-C-4.                        Other NIH Components

Other NIH components shall be responsible for certifying maximum containment (BL4) facilities, inspecting them periodically, and inspecting other recombinant DNA facilities as deemed necessary.

Section IV-D.            Voluntary Compliance

Section IV-D-1.                        Basic Policy - Voluntary Compliance

Individuals, corporations, and institutions not otherwise covered by the NIH Guidelines are encouraged to follow the standards and procedures set forth in Sections I through IV.  In order to simplify discussion, references hereafter to “institutions” are intended to encompass corporations and individuals who have no organizational affiliation.  For purposes of complying with the NIH Guidelines, an individual intending to carry out research involving recombinant DNA is encouraged to affiliate with an institution that has an Institutional Biosafety Committee approved under the NIH Guidelines.

Since commercial organizations have special concerns, such as protection of proprietary data, some modifications and explanations of the procedures are provided in Sections IV-D-2 through IV-D-5-b, Voluntary Compliance, in order to address these concerns.

Section IV-D-2.                        Institutional Biosafety Committee Approval - Voluntary Compliance

It should be emphasized that employment of an Institutional Biosafety Committee member solely for purposes of membership on the Institutional Biosafety Committee does not itself make the member an institutionally affiliated member.  Except for the unaffiliated members, a member of an Institutional Biosafety Committee for an institution not otherwise covered by the NIH Guidelines may participate in the review and approval of a project in which the member has a direct financial interest so long as the member has not been, and does not expect to be, engaged in the project.  Section IV-B-2-a-(4), Institutional Biosafety Committee, is modified to that extent for purposes of these institutions.

Section IV-D-3.                        Certification of Host-Vector Systems - Voluntary Compliance

A host-vector system may be proposed for certification by the NIH Director in accordance with the procedures set forth in Appendix I-II, Certification of Host-Vector Systems.  In order to ensure protection for proprietary data, any public notice regarding a host-vector system which is designated by the institution as proprietary under Section IV-D, Voluntary Compliance, will be issued only after consultation with the institution as to the content of the notice.

Section IV-D-4.                        Requests for Exemptions and Approvals - Voluntary Compliance

Requests for exemptions or other approvals as required by the NIH Guidelines should be submitted based on the procedures set forth in Sections I through IV.  In order to ensure protection for proprietary data, any public notice regarding a request for an exemption or other approval which is designated by the institution as proprietary under Section IV-D-5-a, Voluntary Compliance, will be issued only after consultation with the institution as to the content of the notice.

Section IV-D-5.                        Protection of Proprietary Data - Voluntary Compliance

Section IV-D-5-a.                        General

In general, the Freedom of Information Act requires Federal agencies to make their records available to the public upon request.  However, this requirement does not apply to, among other things, “trade secrets and commercial or financial information that is obtained from a person and that is privileged or confidential.”  Under 18 U.S.C. 1905, it is a criminal offense for an officer or employee of the U.S. or any Federal department or agency to publish, divulge, disclose, or make known “in any manner or to any extent not authorized by law any information coming to him in the course of his employment or official duties or by reason of any examination or investigation made by, or return, report or record made to or filed with, such department or agency or officer or employee thereof, which information concerns or relates to the trade secrets, (or) processes...of any person, firm, partnership, corporation, or association.”  This provision applies to all employees of the Federal Government, including special Government employees.  Members of RAC are “special Government employees.”

In submitting to NIH for purposes of voluntary compliance with the NIH Guidelines, an institution may designate those items of information which the institution believes constitute trade secrets, privileged, confidential, commercial, or financial information.  If NIH receives a request under the Freedom of Information Act for information so designated, NIH will promptly contact the institution to secure its views as to whether the information (or some portion) should be released.  If NIH decides to release this information (or some portion) in response to a Freedom of Information request or otherwise, the institution will be advised and the actual release will be delayed in accordance with 45 Code of Federal Regulations, Section 5.65(d) and (e).

Section IV-D-5-b.                        Pre-submission Review

Any institution not otherwise covered by the NIH Guidelines, which is considering submission of data or information voluntarily to NIH, may request pre-submission review of the records involved to determine if NIH will make all or part of the records available upon request under the Freedom of Information Act.

A request for pre-submission review should be submitted to NIH/OBA along with the records involved to the Office of Biotechnology Activities, National Institutes of Health, 6705 Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD  20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839 (fax).  These records shall be clearly marked as being the property of the institution on loan to NIH solely for the purpose of making a determination under the Freedom on Information Act.  NIH/OBA will seek a determination from the responsible official under DHHS regulations (45 CFR Part 5) as to whether the records involved, (or some portion) will be made available to members of the public under the Freedom of Information Act.  Pending such a determination, the records will be kept separate from NIH/OBA files, will be considered records of the institution and not NIH/OBA, and will not be received as part of NIH/OBA files.  No copies will be made of such records.

NIH/OBA will inform the institution of the NIH Freedom of Information Officer's determination and follow the institution's instructions as to whether some or all of the records involved are to be returned to the institution or to become a part of NIH/OBA files.  If the institution instructs NIH/OBA to return the records, no copies or summaries of the records will be made or retained by DHHS, NIH, or OBA.  The NIH Freedom of Information Officer's determination will represent that official's judgment at the time of the determination as to whether the records involved (or some portion) would be exempt from disclosure under the Freedom on Information Act if at the time of the determination the records were in NIH/OBA files and a request was received for such files under the Freedom of Information Act.

SECTION V.                       FOOTNOTES AND REFERENCES OF SECTIONS I THROUGH IV

Section V-A.  The NIH Director, with advice of the RAC, may revise the classification for the purposes of the NIH Guidelines (see Section IV-C-1-b-(2)-(e), Minor Actions).  The revised list of organisms in each risk group is reprinted in Appendix B, Classification of Human Etiologic Agents on the Basis of Hazard.

Section V-B.  Section III, Experiments Covered by the NIH Guidelines, describes a number of places where judgments are to be made.  In all these cases, the Principal Investigator shall make the judgment on these matters as part of his/her responsibility to "make the initial determination of the required levels of physical and biological containment in accordance with the NIH Guidelines" (see Section IV-B-7-c-(1)).  For cases falling under Sections III-A through III-E, Experiments Covered by the NIH Guidelines, this judgment is to be reviewed and approved by the Institutional Biosafety Committee as part of its responsibility to make an "independent assessment of the containment levels required by the NIH Guidelines for the proposed research" (see Section IV-B-2-b-(1), Institutional Biosafety Committee).  The Institutional Biosafety Committee may refer specific cases to NIH/OBA as part of NIH/OBA's functions to "provide advice to all within and outside NIH" (see Section IV-C-3, ).  NIH/OBA may request advice from the RAC as part of the RAC's responsibility for "interpreting the NIH Guidelines for experiments to which the NIH Guidelines do not specifically assign containment levels" (see Section IV-C-1-b-(2)-(f), Minor Actions).

Section V-C.  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 Laboratories, 5th Edition, 2007.  Copies are available from:  Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402-9371, Phone (202) 512-1800 [http://www.gpo.gov].

Section V-D.  Classification of Etiologic Agents on the Basis of Hazard, 4th Edition, July 1974, U.S. Department of Health, Education, and Welfare, Public Health Service, Centers for Disease Control, Office of Biosafety, Atlanta, Georgia 30333.

Section V-E.  Chin, James ed., Control of Communicable Diseases Manual, 17th Edition, 2000.  ISBN:  087553-242-X, American Public Health Association, 800 I Street, N.W., Washington, D.C. Phone:  (202) 777-2742.

Section V-F.  World Health Organization Laboratory Biosafety Manual, 2nd edition.  1993.  WHO Albany, NY.  Copies are available from:  WHO Publication Centre, USA, (Q Corp) 49 Sheridan Avenue, Albany, New York 12210; Phone:  (518) 436-9686 (Order # 1152213).

Section V-G.  A U.S. Department of Agriculture permit, required for import and interstate transport of plant and animal pathogens, may be obtained from the U.S. Department of Agriculture, ATTN:  Animal and Plant Health Inspection Service (APHIS), Veterinary Services, National Center for Import-Export, Products Program, 4700 River Road, Unit 40, Riverdale, Maryland 20737.  Phone:  (301) 734-8499; Fax:  (301) 734-8226.

Section V-H.  American Type Culture Collection Catalogues of plant viruses, animal viruses, cells, bacteria, fungi, etc. are available from American Type Culture Collection, 10801 University Boulevard, Manassas, VA 20110-2209.  Phone:  (703) 365-2700.

Section V-I.  U.S. Department of Labor, Occupational Safety and Health Administration, 29 CFR 1910.1030, Bloodborne Pathogens.  See also, Exposure to Bloodborne Pathogens, OSHA 3127, 1996 (Revised).

Section V-J.  As classified in the Virus Taxonomy:  The Classification and Nomenclature of Viruses. The Seventh Report of the International Committee on Taxonomy of Viruses, Academic Press, 2000 (0123702003) San Diego, CA.

Section V-K.  i.e., the total of all genomes within a family shall not exceed two-thirds of the genome.

Section V-L.  Organisms including alastrim, smallpox (variola) and whitepox may not be studied in the United States except at specified facilities.  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).