University Policy for Recombinant or Synthetic DNA Biosafety

Western Michigan University recognizes the importance of supporting a broad spectrum of research activities. Cognizant that these activities may be accompanied by some risks, the University requires recombinant or synthetic DNA research activities be reviewed and only be conducted under the auspices of the Institutional Biosafety Committee (IBC). This policy is in full compliance with applicable federal and state laws and regulations. Adherence to this policy shall not exempt the research from compliance with other applicable laws, regulations or policies (e.g., research with human subjects or research with animals). 

Applicability

This policy is applicable to all recombinant or synthetic DNA research, which is conducted at or sponsored by or under the aegis of WMU. No activity involving the construction or handling of recombinant or synthetic DNA molecules or organisms and viruses containing recombinant or synthetic DNA molecules shall be initiated without prior notification, and if necessary review and approval of the WMU Institutional Biosafety Committee unless specifically exempt as described in the regulations.

Coordination with other research compliance regulations

Recombinant or synthetic DNA research projects may sometimes involve other elements that require review and approval prior to the conduct of the research. IBC approval of a recombinant or synthetic DNA research project will always be contingent upon receipt of such approvals and will not be effective until all requisite reviews have been completed and approvals received. The following represent other compliance requirements for research at WMU: 

  • Human Subjects: Human Subjects Institutional Review Board (IRB)
  • Animal Use: Institutional Animal Care and Use Committee (IACUC)
  • Radionuclides: Radiation Safety Committee (RSC)

For further information on any of the requirements of these review systems, contact the associate director of research compliance.

Definition of recombinant and synthetic DNA molecules

In the context of this policy, recombinant and synthetic nucleic acids are defined as:

  1. Molecules that a) are constructed by joining nucleic acid molecules and b) that can replicate in a living cell, i.e., recombinant nucleic acids.
  2. Nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules, i.e., synthetic nucleic acids.
  3. Molecules that result from the replication of those described in (1) or (2) above.

Genomic DNA of plants and bacteria that have acquired a transposable element, even if the latter was donated from a recombinant vector no longer present, are not subject to this policy unless the transposon itself contains recombinant or synthetic DNA.

Recombinant or synthetic DNA biosafety committee

The Institutional Biosafety Committee (IBC) shall be comprised of no less than five members. The committee shall fulfill the responsibilities described in the NIH guidelines for Research Involving Recombinant or Synthetic DNA Molecules (NIH guidelines).

A. Committee membership

The IBC members shall be selected so that they collectively have experience and expertise in recombinant and synthetic DNA technology and the capability to assess the safety of recombinant or synthetic DNA research and to identify any potential risk to public health or the environment. At least two members shall not be affiliated with WMU (apart from membership on the IBC) and shall represent the interest of the Kalamazoo area with respect to the health and protection of the environment. The vice president for research or his/her designee shall be a permanent member of the IBC.

B. Appointment of members

Members of the IBC shall be appointed by the president or his/her designee. A list of recommendations will be made to the president by the IBC. Appointments should be for a period of three years (effective Jan. 1) and initial terms should be staggered so that no more than one-third of them shall expire in any year.

C. Officers

The IBC chair shall be designated by the president or his/her designee and perform those duties normally associated with that office. The biological safety officer for recombinant or synthetic DNA (BSO) shall be designated by the president and perform the duties described in Section Roles and Responsibilities, C, of this policy. The associate director of research compliance shall serve as administrator and will maintain the records of the IBC.

D. Meetings

The IBC shall meet at least once annually. A schedule of meetings shall be publicly posted. Meetings will be open to the public whenever possible, consistent with protection of privacy and proprietary interests. 

A quorum for conducting business shall consist of two-thirds of current members. At least one member not affiliated with WMU (apart from serving on the IBC) must be present.  The meetings will follow recognized parliamentary procedure.

No member may participate in or be involved (except to provide information) in the review or approval of a project in which he or she has been or expects to be engaged or has a direct financial interest.

When additional expertise is required, the IBC may obtain the services of consultants to provide it.

E. Reports

The IBC will present an informational annual report of activity to the vice president for research.

The vice president for research shall file an annual report with NIH/OBA which includes: (i) a roster of all IBC members clearly indicating the chair, contact person, BSO/vice chair, plant expert, and animal expert and (ii) biographical sketch of all IBC members (including community members).

F. IBC records and information

The IBC shall maintain files and records in the office of the associate director of research compliance containing the following information:

  1. The original (not a copy) project registration document submitted by the principal investigator for review by the IBC.
  2. Correspondence related to specific recombinant or synthetic DNA research activities.
  3. Copies of RAC, NIH/OBA and/or FDA decisions, as applicable.
  4. Proceedings related to renewal, modification, or termination of research projects.
  5. Copies of agenda and minutes of IBC meetings, along with detailed comments on projects reviewed and decisions of the IBC.
  6. Documentation of IBC membership, including credentials and training of current members.
  7. Copies of reports and correspondence related to problems, violations of NIH guidelines, accidents, and illnesses related to research projects.

Experimental classes and procedures

The different classes of experiments and particular constraints applying to each (e.g., containment requirements) are found in the NIH guidelines for Research Involving Recombinant or Synthetic DNA Molecules (NIH guidelines). The latest Amendment to the NIH guidelines was published in the April, 2016, issue of the Federal Register. The current NIH guidelines are available online or upon request from the associate director of research compliance. As these regulations are modified by subsequent agency action, those modifications shall be incorporated into this policy. A summary description of each class of experiment and the associated required procedures are outlined in the following subsections.

A. Experiments that require IBC approval, Recombinant DNA Advisory Committee (RAC) review, and NIH director approval before initiation

Experiments in this class cannot be initiated without submission of relevant information on the proposed experiment to the Office of Biotechnology Activities (NIH/OBA), the publication of the proposal in the Federal Register for 15 days of comment, review by the RAC, and specific approval by the NIH. The containment conditions or stipulation requirements for such experiments will be recommended by RAC and set by NIH at the time of approval. Such experiments require IBC approval before initiation. Definitions and examples are presented in Section III-A of the NIH guidelines.

B. Experiments that require NIH/OBA and IBC approval before initiation

Experiments in this class cannot be initiated without submission of relevant information on the proposed experiment to NIH/OBA. The containment conditions for such experiments will be determined by NIH/OBA in consultation with ad hoc experts. Such experiments require IBC approval before initiation. Definitions and examples are presented in Section III B of the NIH guidelines.

C. Experiments that require IBC and HSIRB approvals and RAC review before research participant enrollment

Research proposals involving the deliberate transfer of recombinant or synthetic DNA, or DNA or RNA derived from recombinant or synthetic DNA, into human subjects (human gene transfer) will be considered through a review process involving NIH/OBA and RAC. Experiments in this class cannot be initiated without submission of relevant information on the proposed human gene transfer experiments to NIH/OBA and RAC for review and approval, Investigational New Drug (IND) application submission to FDA, and application for review and approval by the IBC. Approval must also be obtained from the WMU Human Subjects Institutional Review Board (HSIRB) and the IBC and IRB of each institution at which recombinant or synthetic DNA material will be administered to human subjects. The submission, review, and approval process is detailed in Section III-C of the NIH guidelines.

D. Experiments that require IBC approval before initiation

Experiments in this class require submission of a registration document to the IBC for review and approval prior to initiation of the experiments. Definitions and examples are presented in Section III-D of the NIH guidelines. Practices for the physical and biological containment for recombinant or synthetic DNA research involving plants are specified in Appendix P of the NIH guidelines; practices for the physical and biological containment for recombinant or synthetic DNA research involving animals are specified in Appendix Q of the NIH guidelines.

E. Experiments that require IBC notice simultaneous with initiation

Experiments in this class require submission of a registration document to the IBC at the time of initiation of the experiments. Definitions and examples are presented in Sections III-E of the NIH guidelines. Approval by the IBC prior to initiation is not required unless the IBC determines the investigator has incorrectly classified the experiments.

F. Experiments in this class are exempt from the NIH guidelines

Experiments in this class are exempt from the NIH guidelines: however, registration with the WMU IBC is required.  In addition, other federal and state standards of biosafety may still apply to such research (for example, the Centers for Disease Control and Prevention (CDC)/NIH publication Biosafety in Microbiological and Biomedical Laboratories). Definitions and examples are presented in Sections III-F of the NIH guidelines. 

Research facility biohazard warning signs

A. Biosafety Level 1 (BL1) Facilities 

A biohazard sign must be posted on the entrance to the laboratory or facility whenever infectious agents are present. The sign must include the name of the agent(s) in use and the name and telephone number of the principal investigator.

B. Biosafety Level 2 (BL2) Facilities

A biohazard sign must be posted on the entrance to the laboratory or facility when etiologic agents are in use. The sign must include the name of the agent(s) in use, the biosafety level, the required immunizations, the name and telephone number of the principal investigator, any personal protective equipment that must be worn in the laboratory or facility, and any procedures required for exiting the laboratory or facility.

C. Biosafety Level 3 (BL3) or Biosafety Level 4 (BL4) Facilities

When infectious materials or infected animals are present in the laboratory, facility, or containment module, a hazard warning sign, incorporating the universal biohazard symbol, must be posted on all laboratory/facility and animal room access doors. The hazard sign must identify the agent(s) in use, list the names and telephone numbers of the principal investigator and other responsible person(s) (including the biological safety officer for recombinant or synthetic DNA, the animal facility manager, if applicable, and the associate director of research compliance), and indicate any special requirements for entering the laboratory or facility, such as the need for immunizations, respirators, or other personal protective measures.

Forms and project registration procedures

A. Registration for recombinant or synthetic DNA research

The project registration form delineating the required relevant information for notification and/or review is available online or upon request from the associate director of research compliance. Project registration forms, which are obtained online must be completed, signed, and paper copies submitted to the associate director of research compliance for review by the IBC. It is not possible, at this time, to submit project registration forms electronically. Project registration forms must be completed and resubmitted annually to the IBC for each project involving recombinant or synthetic DNA molecules.

B. Registration and review procedures

  1. Investigators will be notified via email by the IBC of the next scheduled meeting and the deadline for submission of the registration form for each project to be reviewed at that time. This notification will include instructions to be used to access online forms. The IBC will also provide each investigator with a copy of the most current NIH guidelines and WMU Policy for Recombinant or Synthetic DNA Biosafety (this policy) to assist in the completion of the registration document.
  2. The principal investigator must complete and sign one registration form for each new or continuing project to be reviewed by the IBC. For each project, only one individual may function as the principal investigator and must take responsibility for that project and its compliance with the NIH guidelines and this policy.
  3. After the principal investigator has signed the project registration form, the principal investigator must obtain the signature of his/her department chair and/or unit director on the project registration form. After the department chair and/or unit director has signed the project registration form, the principal investigator must submit the original project registration form and the prescribed number of copies to the associate director of research compliance. Project registration forms lacking one or more original signatures cannot be accepted for IBC review.
  4. All project registration forms must be submitted to the associate director of research compliance. The submission for each project must include the original registration document (with the original signature of the principal investigator and his/her department chair and/or unit director) and the prescribed number of copies as indicated on the project registration form. The associate director of research compliance assigns each project a unique number and distributes the copies to the members of the IBC for review.
  5. At a convened meeting, the IBC reviews all project registration forms submitted since its last meeting.
  6. The IBC will notify the principal investigator in writing of the results of the committee’s review. The IBC may approve or disapprove a project or may make recommendations for revisions which would lead to approval.

Roles and responsibilities 

The safe conduct of experiments involving recombinant or synthetic DNA depends on the individual conducting such activities. It is beyond the scope of this policy to anticipate every possible situation. Motivation and good judgment are the key essentials to protection of health and the environment. The Western Michigan University Policy for Recombinant or Synthetic DNA Biosafety (this policy) in conjunction with the NIH guidelines is intended to assist the Institutional Recombinant or Synthetic DNA Biosafety Committee, biological safety officer for recombinant or synthetic DNA, and the principal investigator in determining safeguards that should be implemented. It is the responsibility of Western Michigan University (and the Institutional Biosafety Committee acting on its behalf) to adhere to the intent of the NIH guidelines and to ensure that recombinant or synthetic DNA activities comply with the NIH guidelines. The roles and responsibilities, as outlined in the NIH guidelines, constitute an administrative framework in which safety is an essential and integral part of research involving recombinant or synthetic DNA molecules.

A. Responsibilities of the Institution (Western Michigan University)

  1. Establish and implement policies that provide for the safe conduct of recombinant or synthetic DNA research and that ensure compliance with the NIH guidelines.
  2. Establish and maintain an Institutional Biosafety Committee (IBC) that meets the requirements and carries out the functions outlined in Section Forms and Project Registration Procedures, B, of this policy (Sections IV-B-2-a and IV-B-2-b of the NIH guidelines).
  3. Appoint a biological safety officer for recombinant or synthetic DNA (BSO) who shall be a member of the IBC and carry out the duties specified in Section Forms and Project Registration Procedures, C, of this policy (Section IV-B-3 of the NIH guidelines).
  4. Appoint an expert in plant, plant pathogen, or plant pest containment principles who shall be a member of the IBC.
  5. Appoint an expert in animal containment principles who shall be a member of the IBC.
  6. Ensure that when the Institution participates in or sponsors recombinant or synthetic DNA research involving human subjects:  (i) the IBC has adequate expertise and training (using ad hoc consultants as deemed necessary), and (ii) all aspects of Appendix M of the NIH guidelines have been appropriately addressed by the principal investigator prior to submission to NIH/OBA.
  7. Assist and ensure compliance with the NIH guidelines by principal investigators conducting research at the Institution.
  8. Ensure appropriate training for the IBC chair and members, BSO and other containment experts, principal investigators, and laboratory staff regarding laboratory safety and implementation of the NIH guidelines and ensuring that the principal investigator has sufficient training.
  9. Determine the necessity for health surveillance of personnel involved in connection with individual recombinant or synthetic DNA projects, and if appropriate, conduct a health surveillance program for such projects; establish and maintain a health surveillance program for personnel engaged in large scale research or production activities involving viable organisms containing recombinant or synthetic DNA molecules and for personnel engaged in animal research involving viable recombinant or synthetic DNA-containing microorganisms which require BL3 or greater containment at the laboratory scale.

B. Responsibilities of the Recombinant or Synthetic DNA Biosafety Committee

The IBC chair is responsible for ensuring that the IBC members are appropriately trained and qualified for appointment to the IBC and for recommending continued training for IBC members as needed to fulfill the responsibilities of IBC membership as outlined below.

On behalf of the Institution, the Institutional Biosafety Committee (IBC) shall:

  1. Review recombinant or synthetic DNA research conducted at or sponsored by the Institution for compliance with the WMU Policy for Recombinant or Synthetic DNA Biosafety (this policy) and with 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 or synthetic DNA research, and (iii) ensuring compliance with all surveillance, data reporting, and adverse event reporting required by the NIH guidelines.
  2. Notify the principal investigator in writing of the results of the IBC’s review; the IBC may approve or disapprove a project or may make recommendations for revisions which would lead to approval.
  3. Lower containment levels for certain experiments as specified in Section III D-2-a of the NIH guidelines.
  4. Set containment levels as specified in Sections III-D-4-b and III-D-5 of the NIH guidelines.
  5. Periodically review recombinant or synthetic DNA research conducted at Western Michigan University to ensure compliance with the NIH guidelines and the WMU Policy for Recombinant or Synthetic DNA Biosafety (this policy).
  6. Adopt emergency plans covering accidental spills and personnel contamination resulting from recombinant or synthetic DNA research.
  7. The IBC may not authorize initiation of experiments, which are not explicitly covered by the NIH guidelines until NIH (with the advice of RAC) establishes the containment requirement.

C. Responsibilities of the biological safety officer for recombinant or synthetic DNA (BSO)

  1. Conduct periodic inspections to ensure that laboratory standards for recombinant or synthetic DNA research are rigorously followed.
  2. Develop emergency plans for handling accidental spills and personnel contamination and investigating laboratory accidents involving recombinant or synthetic DNA research.
  3. Provide advice on laboratory security related to recombinant or synthetic DNA research activities.
  4. Provide technical advice to principal investigators and the IBC on research safety procedures.
  5. Serve as vice chair of the IBC. 

D. Responsibilities of department chairs and/or unit directors

  1. Provide departmental approval for the principal investigator to conduct the work specified in the project registration form.
  2. Determine that the facilities and procedures proposed in the project registration form are adequate for the safe conduct of the research and the safety of other personnel—faculty, staff, and visitors—using the facilities within which the research is conducted.
  3. Ensure the continued safety and security during the conduct of the research, along with strict compliance with the NIH guidelines and the WMU Policy for Recombinant or Synthetic DNA Biosafety (this policy).

E. Responsibilities of the principal investigator

On behalf of the Institution, the principal investigator is responsible for full compliance with the NIH guidelines in the conduct of recombinant or synthetic DNA research. As part of this general responsibility, the principal investigator shall:

  1. Adhere to IBC-approved requirements for posting biohazard warning signs on the entrance to his/her laboratory as outlined in Section Research Facility Biohazard Warning Signs of this policy.
  2. Initiate or modify no recombinant or synthetic DNA research until that research or the proposed modification thereof has been reviewed and approved by the IBC and has met all other requirements of the NIH guidelines.
  3. Determine which class of the NIH guidelines for covered experiments apply to the proposed research and ensure that appropriate procedures are followed in completing the registration document for IBC project review.
  4. Report any new information bearing on the NIH guidelines to the IBC and to NIH/OBA.
  5. Be adequately trained in good microbial techniques and ensure that laboratory staff are appropriately trained.
  6. Adhere to IBC-approved emergency plans for handling accidental spills and personnel contamination.
  7. Comply with shipping requirements for recombinant or synthetic DNA molecules specified in Appendix H of the NIH guidelines.

For submissions by the principal investigator to NIH/OBA, the principal investigator shall: 

  1. Submit information to NIH/OBA, with notice to the IBC, for certification of new host-vector systems.
  2. Petition NIH/OBA, with notice to the IBC, for proposed exemptions to the NIH guidelines.
  3. Petition NIH/OBA, with concurrence of the IBC, for approval to conduct experiments specified in Sections III-A-1 and III-B of the NIH guidelines.
  4. Petition NIH/OBA, with notice to the IBC, for determination of containment for experiments requiring case-by-case review.
  5. Petition NIH/OBA, with notice to the IBC, for determination of containment for experiments not explicitly covered by the NIH guidelines.
  6. Ensure that all aspects of Appendix M of the NIH guidelines have been appropriately addressed prior to the submission of human genotherapy experiments to NIH/OBA.
  7. Submit a completed and signed project registration form to the associate director of research compliance for IBC review including all information and correspondence received from NIH/OBA.

Note: Approval of a research project or other information from NIH/OBA is not a substitute for IBC approval to conduct the research.

For submissions by the principal investigator to the IBC, the principal investigator shall:

  1. Make an initial determination of the required levels of physical and biological containment in accordance with the NIH guidelines.
  2. Select appropriate microbiological practices and laboratory techniques to be used for the research.
  3. Submit the initial research protocol and any subsequent changes to the associate director of research compliance who will forward the protocol to the IBC for review and approval or disapproval.
  4. Remain in communication with the IBC throughout the conduct of the project.

Prior to initiating research, the principal investigator shall:

  1. Make available to all laboratory staff the protocols that describe the potential biohazards and the precautions to be taken.
  2. Instruct and train laboratory staff in (i) the practice and techniques required to ensure safety, and (ii) the procedures for dealing with accidents.
  3. Inform the laboratory staff of the reasons and provisions for any precautionary medical practices advised or requested (e.g., vaccinations or serum collection).

During the conduct of the research, the principal investigator shall:

  1. Supervise the safety performance of the laboratory staff to ensure that the required safety practices and techniques are employed.
  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 for recombinant or synthetic DNA (BSO), greenhouse/animal facility manager (if applicable), the RDBC, NIH/ORDA, and other appropriate authorities.
  3. Correct work errors and conditions that may result in the release of recombinant or synthetic DNA materials.
  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).
  5. Comply with reporting requirements for human gene transfer experiments conducted in compliance with the NIH guidelines.

Procedures for reporting adverse issues to NIH/OBA

Western Michigan University recognizes the importance of reporting any significant problems, violations of the NIH guidelines, or any significant research-related accidents and illnesses to NIH/OBA within 30 days. Such reporting is the responsibility of the Institution, the Institutional Biosafety Committee (IBC), the biological safety officer for recombinant or synthetic DNA (BSO), and each principal investigator.

Information concerning noncompliance with the NIH guidelines may be brought forward by any person. It should be delivered to both NIH/OBA and the Institution (WMU). Western Michigan University, generally through the IBC, shall take appropriate action and shall forward a complete report of the incident recommending any further action to the NIH/OBA.

Whenever possible, the following procedures will be followed:

A. Immediately following the problem, violation, accident or illness, the principal investigator must notify the biological safety officer for recombinant or synthetic DNA (BSO) and the greenhouse/animal facility manager, if applicable.

B. Within seven days of notification by the principal investigator, the biological safety officer for recombinant or synthetic DNA (BSO) must notify the Institutional Biosafety Committee (IBC). If necessary, an emergency meeting of the IBC may be convened to discuss the report.

C. Within seven days of notification by the biological safety officer for recombinant or synthetic DNA (BSO), the Institutional Biosafety Committee (IBC) must submit a written report of the problem, violation, accident, or illness to the vice president for research.

D. Within seven days of submission of the written report from the Institutional Biosafety Committee (IBC), the vice president for research, on behalf of the Institution, shall file a formal report with NIH/OBA detailing the incident.