Institutional Biosafety Committees (IBCs) were established under the NIH Guidelines for Research Involving Recombinant DNA Molecules. IBCs are intended to provide local review and oversight of research utilizing recombinant DNA. The Marshfield Clinic Institutional Biosafety Committee, along with the Marshfield Clinic Research Institute Safety Liaison or Institutional Biosafety Officer (IBO), assist researchers and research staff in observing safe biological laboratory practices, and endeavor to ensure that recombinant DNA and CDC-defined Biosafety Level 3 or 4 pathogen research is carried out in secure facilities, and in compliance with applicable regulations and guidelines.

Over time, many institutions have chosen to assign IBCs the responsibility of reviewing a variety of experimentation involving biological materials (e.g., infectious agents) and other potentially hazardous agents (e.g., carcinogens). This additional responsibility is assigned entirely at the discretion of the institution.

IBC members have the Operating Procedures document available to them for guidance. Please Contact ORIP at (715) 389-3022 with questions. 

Operating Procedures

Responsibility /Authority


Recombinant DNA Responsibilities

The IBC is responsible for the following activities related specifically to the requirements contained within the NIH Guidelines for Research Involving Recombinant DNA Molecules:

  1. Reviewing recombinant DNA research conducted at or sponsored by the institution for compliance with the NIH Guidelines, and approving those research projects that are found to conform with the NIH Guidelines. The review shall include:
    1. An independent assessment of the containment levels required by the NIH Guidelines for the proposed research
    2. An assessment of the facilities, procedures, practices, and training and expertise of personnel involved in recombinant DNA research;
    3. Ensuring that all aspects of Appendix M (of the Guidelines) have been appropriately addressed by the principal investigator;
    4. Ensuring that no research participant is enrolled in a human gene transfer experiment until the Recombinant DNA Advisory Committee (RAC) review process has been completed;
    5. 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;
    6. Ensuring that final IBC approval is granted only after the RAC review process has been completed; and
    7. Ensuring compliance with all surveillance, data reporting, and adverse event reporting requirements as required by the NIH Guidelines.

  2. Notifying principal investigators of the results of the IBC’s review.

  3. Lowering containment levels for certain experiments as specified in Section III-D-2-a of the NIH Guidelines entitled, Experiments in which DNA from Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Euakryotic Host Vector Systems.

  4. Setting containment levels as specified in Section III-D-4-b of the NIH Guidelines titled, Experiments Involving Whole Animals and Section III-D-5, Experiments Involving Whole Plants.

  5. Periodically reviewing recombinant DNA research conducted at the institution to ensure compliance with the NIH Guidelines.

  6. Adopting emergency plans covering accidental spills and personnel contamination resulting from recombinant DNA research.

  7. Reporting any significant problems with or violations of the NIH Guidelines and any significant research-related accidents or illnesses to the Director of Medical Research and NIH/Office of Biotechnology Activities within 30 days, unless the IBC determines a report has already been filed by the principal investigator

The IBC may not authorize initiation of experiments which are not explicitly covered by the NIH Guidelines until NIH (with the advice of RAC when required) establishes the containment requirement.

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Other Responsibilities

Additional responsibilities of the IBC, as assigned by the Director of Medical Research, include:

  1. Prior review and approval of research activities involving Biosafety Level 3 or 4 agents
  2. Review of periodic inspection reports prepared by the MCRI Safety Liaison or Institutional Biosafety Officer (IBO).
  3. Providing advice to investigators and the Director of Medical Research on laboratory security, research safety procedures and training activities.
  4. Recommendations proposed by Marshfield Clinic’s Safety Committee, which directly impact MCRI, may be submitted to the IBC by the Director of Medical Research for Committee input.
  5. Investigating all concerns regarding biosafety issues expressed by staff, employees, or the general public.

The IBC has the authority to approve, require modifications before approval, or withhold approval of proposals submitted for review. Applications and proposals that have been approved by the IBC may be subject to further appropriate review and approval. (e.g., IRB, IACUC, Institutional approval). However, bodies alone may not allow an activity involving the use of recombinant DNA or CDC-defined Biosafety Level 3 or 4 pathogens to go forward if it has not been approved by the IBC.

The IBC is authorized to suspend an activity involving recombinant DNA or other CDC-defined Biosafety Level 3 or 4 pathogens that it previously approved if it determines that the activity is not being conducted in accordance with the description of that activity provided by the principal investigator and approved by the Committee.

The IBC and the MCRI Safety Liaison or Institutional Biosafety Officer (IBO) will assist all researchers and research staff in observing safe biological laboratory practices, and endeavors to assure that recombinant DNA and CDC-defined Biosafety Level 3 or 4 pathogen research is carried out in secure facilities in compliance with all regulations. In fulfilling this responsibility, the Committee will make a reasonable effort to ensure that all individuals involved in the use of recombinant DNA and CDC-defined Biosafety Level 3 or 4 pathogens understand their individual and collective responsibilities as well as applicable laws and regulations pertaining to the safe handling, storage, and disposition of these

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Membership

Members will be appointed by the Director of Medical Research in consultation with the Director of Research Integrity and Protections and/or Institutional Biosafety Officer (IBO), for a term of three years. Terms may be renewable with no limit to the number of terms a member may serve. In order to ensure continuity, the length of the terms of members appointed in the inaugural year will be staggered. Committee members, through their collective experience and expertise, shall be deemed qualified to assess the safety of recombinant DNA and other CDC-defined Biosafety Level 3 or 4 pathogen research and to identify any potential risk to public health or the environment. Committee membership will, at a minimum, consist of five members, including:

  1. at least two members who are not affiliated with the institution and who represent the interest of the community with respect to health and protection of the environment.
  2. at least one individual with expertise in plant, plant pathogen, or plant pest containment principles.
  3. at least one scientist with expertise in animal containment principles.
  4. a biological safety officer (required when an institution conducts recombinant DNA research at BL3, BL4, or large scale [greater than 10 liters]).
  5. Marshfield Clinic Research Institute’s safety liaison to Marshfield Clinic’s general safety committee

Individuals in the following areas will be given priority when considering additional members:

  1. an individual with expertise in recombinant DNA technology, biological safety, and physical containment.
  2. an individual (or consultant(s) to the committee) who is knowledgeable in institutional commitments and policies, applicable laws, standards of professional conduct and practice, community attitudes, and the environment.
  3. an individual who represents the MCRI laboratory technical staff.

One member may serve more than one of these roles, as long as the committee has no fewer than five members. The IBC Chairman will be appointed by the Director of Medical Research, from among the membership, for a one-year term, renewable annually. No limitation on terms of Chairmanship shall exist. The Chairman must be familiar with the needs and requirements of MCRI researchers as well as any applicable federal, state, and local laws and/or guidelines. A Co-chairman will be appointed at the discretion of the Chairman, from among the membership.

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Experiments Covered by NIH Guidelines

There are six categories of experiments involving recombinant DNA. The six categories are designated based on the required approvals from various combinations of five different entities.

  1. Experiments requiring approval of the IBC, the Recombinant DNA Advisory Committee (RAC) of the Department of Health and Human Services, and the director of NIH prior to initiation of the experiment. This category regulates the deliberate transfer of drug resistance traits to microorganisms.
  2. Experiments requiring the approval of the Office of Biotechnology Activities (OBA) at NIH and the IBC prior to initiation. This category regulates the cloning of toxin molecules with an LD50 of less than 100 ng/kg of body weight.
  3. Experiments requiring the approval of the IBC and the Institutional Review Board (IRB) as well as RAC review before research participant enrollment. This category regulates the transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA into human subjects
  4. Experiments requiring the approval of the IBC prior to initiation. This category regulates several types of experiments:
    1. Experiments using Risk Group 2, 3, 4 or restricted agents (see below) as host vector systems
    2. Experiments in which DNA from Risk Group 2, 3, 4 or restricted agents are cloned into nonpathogenic prokaryotic or lower eukaryotic host-vector systems
    3. Experiments involving the use of infectious DNA or RNA viruses or defective DNA or RNA viruses in the presence of helper virus in tissue culture systems
    4. Experiments that may generate transgenic animals or plants which may extend the host-range of human or animal pathogens, or that involve risk group 2, 3, or 4 containment, i.e. experiments involving the use of eukaryotic virus vectors in whole animals or the development of genetically engineered plants
    5. Experiments involving more that 10 liters of culture of recombinant organisms
  5. Experiments requiring notification of the IBC simultaneous with initiation. This category regulates recombinant DNA activities not designated in the previous categories and generally refers to recombinant techniques in nonpathogenic prokaryotes and lower eukaryotes. Included are experiments (1) using vectors less than two-thirds of the genome of defective animal or plant viruses, free of helper virus, (2) cloning DNA for more than one-half of the genome of risk group 1 or 2 human or animal pathogens, or cloning of known oncogenes (3) generating transgenic animals requiring ABL-1 containment, (4) involving whole plants, (5) not specified on this sheet (the “catch-all” category).
  6. Experiments exempt from NIH guidelines. The following recombinant DNA molecules are exempt
    1. Those not in organisms or viruses
    2. Those that consist entirely of DNA segments from a single nonchromosomal or viral DNA source
    3. Those that consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses when propagated only in that host (or closely related strain of the same species), or when transferred to another host by well-established physiological means (i.e. bacterial conjugation)
    4. Those that consist entirely of DNA from a eukaryotic host including its chloroplasts, mitochondria, or plasmids (but excluding viruses) when propagated only in that host (or closely related strain of the same species)
    5. Those that consist entirely of DNA segments from different species that exchange DNA by known physiological processes, though one or more segments may be synthetic equivalent. A list of such exchangers will be prepared and periodically revised by the NIH director with the advice of the RAC after appropriate notice and opportunity for public comment
    6. Those that present no significant risk to health or the environment, as determined by the NIH director with the advice of the RAC after appropriate notice and opportunity for public comment. Examples of exemptions are: (a) the cloning of DNA in E. coli K12. S. cervisiae, and B. subtilis host-vector systems (with the exception of DNA from risk group 2, 3, or 4 pathogens), (b) the purchase or transfer of transgenic rodents.

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IBC Procedures - New Proposal Review Process


Experiments requiring approval of IBC prior to initiation

Proposals for activities involving recombinant DNA or other CDC-defined Biosafety Level 3 or 4 pathogens may be submitted at any time and must be accompanied by an application form.

All protocols will be given an initial review by the IBO or IBC Chair, as appropriate. The IBO or IBC Chair will determine whether review by the IBC is necessary. If the IBO or IBC Chair finds that no extramural body has conducted a scientific merit review of the protocol and feels that the Institutional Biosafety Committee does not have the membership to be able to conduct an adequate scientific merit review, the protocol will be sent to the Research Committee for an evaluation.

The IBC will make every attempt to review protocols at a convened meeting within 30 days of receipt of an application. Whenever possible, applications will be distributed to the membership a minimum of one week in advance of the meeting. All members will be expected to review the protocol, discuss any concerns with the investigator prior to the meeting, and be prepared to recommend approval, modification, or disapproval at the convened meeting. Those members who are unable to attend the convened meeting are encouraged to submit their comments in writing to the Office of Research Integrity and Protections.

Approval of the research project will be granted only after review at a convened meeting of a quorum (a majority of the membership who do not have a conflict of interest) of the IBC and with the approval vote of a majority of the members present. When approving a research project, the Committee will use the following criteria, including but not limited to:

  1. Is the Biosafety level appropriate?
  2. Is the investigator qualified to conduct the research?
  3. Are appropriate training procedures in place for other staff proposed to be involved?
  4. Are appropriate containment procedures in place?
  5. Are disposal procedures appropriate?
  6. Are facilities/equipment adequate to conduct the research safely?

No member of the IBC may be involved (except to provide information requested by the IBC) 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. A member who has a conflicting interest cannot contribute to the constitution of a quorum.

The Office of Research Integrity and Protections is responsible for notifying the investigator in writing of the IBC’s decision to approve or withhold approval, or of modifications required to secure IBC approval. If the IBC decides to withhold approval of an activity, it will include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in writing. The IBC may reconsider its decision in light of the information provided by the investigator. The researcher may proceed with the project after written approval is received.

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Experiments requiring notification to IBC simultaneous to initiation

The review process will be the same as the process for those experiments requiring IBC approval prior to initiation. However, the investigator may begin his/her research at the same time an application is filed with the IBC. The investigator may, however, be asked to modify or terminate his/her research if the IBC finds concerns after its review.

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Experiments requiring a declaration of use.

On a yearly basis, lab directors will be required to submit a declaration of all BSL2 and above agents currently being stored or utilized. This information should be provided concurrently with laboratory inspections.

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Amendments

Any changes in project design involving recombinant DNA or CDC-defined biosafety level 3 or 4 pathogens require that an amended application be submitted to the IBC. If the research fell within a category that required notification rather than prior review, the change can be initiated at the same time the amended application is submitted to the IBC. If the research fell within a category that required prior review and approval by the IBC, the change cannot take place until IBC notification of approval of the amendment has been received by the investigator.

All protocol amendments will initially be reviewed by the IBO or IBC Chair. If the IBO or IBC Chair determines the change to be non-significant, the IBO or IBC Chair may grant preliminary approval of the change, and the investigator may implement the change. The investigator will be notified that they have preliminary approval, and that this approval could be withdrawn within the next two-week period. At the same time, the amendment will be sent to all committee members. Any member who has a concern with the amendment may request that a committee meeting be held for the purpose of reviewing the amendment. If no committee member requests a full committee meeting within two weeks of distribution of the amendment, the investigator will be notified that full approval is granted. If full committee review is requested, the investigator will be notified that a full review has been requested. Approval of the amendment will be granted after review at a convened meeting of the quorum of the IBC and with an approval vote of a majority of the quorum present. If the amendment is not approved by a majority of the quorum present, the investigator will be notified that the previously granted preliminary approval has been withdrawn and he/she may not implement the change.

If the change is determined to be significant, the amendment will be sent to the entire IBC membership, through the mail, along with preliminary comments from the IBO or IBC Chair. No preliminary approval by the IBO or IBC Chair will be granted. Each member will have two weeks to review the amendment, indicate his or her approval, disapproval, or conditional approval, and return the amendment to the Office of Research Integrity and Protections. Members with questions are encouraged to discuss them with the investigator and share the response with all committee members. An amendment is considered approved when a majority of members indicate their approval.

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Continuing Review

The IBC shall conduct continuing reviews of previously approved activities at appropriate intervals as determined by the IBC, but not less than once each year. A request for an updated application will be sent to investigators by the Office of Research Integrity and Protections prior to the expiration of the approval period as set by the IBC.

Continuing reviews will be initially reviewed by the IBO or IBC Chair. If the IBO or IBC Chair determines that the project is progressing with no change in the protocol, the IBO or IBC Chair may approve continuation of the project. If the IBO or IBC Chair determines that there has been a change in the protocol, the continuing review will be sent to the entire IBC membership, through the mail, along with preliminary comments from the IBO or IBC Chair. Each member will have two weeks to review the report, indicate his or her approval, disapproval, or conditional approval, and return the report to the Office of Research Integrity and Protections. Members with questions are encouraged to discuss them with the investigator and share the response with all committee members. A continuing review is considered approved when a majority of members indicate their approval for continuation.

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Review of Concerns

The IBO or IBC Chair shall review, and if warranted, investigate any concerns surrounding the use of Recombinant DNA or other CDC-defined Biosafety Level 3 or 4 pathogens raised by staff, employees, or the general public. The IBO’s or IBC Chair’s findings will be reported to the IBC, and if the IBC concurs with those finding, a report will be forwarded to the Director of Medical Research through the Office of Research Integrity and Protections.

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Activity Suspension

The IBC may suspend an activity involving recombinant DNA or other CDC-defined Biosafety Level 3or 4 pathogens if it determines that the activity is not being conducted in accordance with the description of that activity provided by the principal investigator and approved by the Committee. The IBC may suspend an activity only after review of the matter at a convened meeting of a quorum of the IBC and with the suspension vote of a majority of the quorum present. The Director of Medical Research will receive notice of any suspension.

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Recordkeeping

The IBC, through the Office of Research Integrity and Protections, will maintain for a period of at least three years minutes of IBC meetings, including records of attendance, activities of the committee, and committee deliberations. The Office of Research Integrity and Protections will also maintain for a period of three years past the termination of each project, all records of applications, proposals, and proposed significant changes in activities involving recombinant DNA or other CDC-defined Biosafety Level 3 or 4 pathogens. All records shall be accessible for inspection and copying by authorized institutional officials.

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