1. The University of Toledo Institutional Biosafety Committee (IBC) The following slides are presented as frequently asked questions regarding the role of the IBC and what types of research require UT personnel to submit research protocols for approval by the IBC Last updated 22 Feb. 20161

2. What is the purpose/mission of the IBC? The primary mission of the IBC is to ensure the safety of staff, students, and patients involved in biological research at our university, and also to protect the general public and the environment from adverse consequences related to that research This includes meeting all required standards set by federal, state and local governments, and as necessary, development of University of Toledo-specific policies to make any research conducted with hazardous, or potentially hazardous, biologic agents (either naturally occurring or synthetically created) “as safe as possible” Last updated 22 Feb. 20162

3. What are the edicts that guides the activities of the IBC? NIH Requirements for IBCs NIH Guidelines for Research Involving Recombinant and Synthetic Nucleic Acids, issued by the NIH Office of Biotechnology Activities (NIH OBA) NIH Guidelines for Research Involving Recombinant and Synthetic Nucleic Acids Biosafety in Microbiological and Biomedical Laboratories (BMBL), issued by CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL) OSHA Blood-borne Pathogens Standard CDC/USDA Select Agent regulations: 42 CFR 73, 7 CFR 331 CDC/USDA Select Agent regulations Last updated 22 Feb. 20163

4. What types of research need an IBC-approved research protocol? Any research utilizing the following need IBC approval before performing research on or receiving biological materials at UT: Recombinant DNA Synthetic nucleic acids UNLESS they pass all 3 criteria below: – Can neither replicate nor generate nucleic acids that can replicate in any living cell (e.g., oligonucleotides or other synthetic nucleic acids that do not contain an origin of replication or contain elements known to interact with either DNA or RNA polymerase) – Are not designed to integrate into DNA – Do not produce a toxin that is lethal for vertebrates at an LD 50 of less than 100 nanograms per kilogram body weight Microbial agents (BSL1 level and higher) Biological toxins Animal (including human) tissues and cell lines Nanomaterials with biological properties Select agents and toxins Last updated 22 Feb. 20164

5. Diagram showing information regarding work within the different categories of the NIH Guidelines* Nanomaterials are not represented on this diagram *NIH Section: NIH Guidelines for Research Involving Recombinant & Synthetic Nucleic Acids NIH Guidelines for Research Involving Recombinant & Synthetic Nucleic Acids EHRS: Environmental Health and Radiation Safety (University of Toledo) OBA: Office of Biotechnology Activities SNA: synthetic nucleic acids Last updated 22 Feb. 20165 Select Agent or Toxin Animals Non-SAT BSL3 rDNA Animals Animals, III-D Rodents, III-E-3 Rodents, III-F-8, App C BSL1 BSL2 BSL3 Exempt per NIH NIH-OBA CDC BSL External Authority Type of Work TBD NIH- OBA/ RAC, FDA IBC, IRB R.O.; IBC Internal Oversight BBP (MIOSHA) BMBL (CDC) IBC, EHRS) IBC, (EHRS)) IBC, (EHRS) Exempt rDNA/SNA, NIH Guidelines Sections III-F-1 thru III-F-8; Appendix C UT requires IBC protocol Non-pathogenic prokaryotes and non-pathogenic eukaryotes rDNA with <2/3 eukaryotic viral genome and no helper, in tissue culture only NIH Section III-E NIH Section III-F and App C NIH Section III-D RG2 or RG3 agents used in host-vector systems including pathogenic bacteria; viral vectors; rDNA administered to whole animals (fish, worms, flies, rodents) Non-recomb. pathogens (isolated for study) Non-recomb. biological toxins include below- threshold SATs. Human blood, body fluids, or tissues used in research Some types of animal tissues, blood, fluids (define) used in research Human cell lines? (define) Human Gene Transfer or infectious agents administered to humans Section III-A, Section III-B: NIH and IBC approval and before initiation NIH-OBA TBD

6. How do I initiate an IBC protocol? Submit the protocol by the last Friday of the month prior to the review meeting (for example, if you want the protocol reviewed at the 12/17/15 meeting, the deadline for submitting would be 11/27/15. The IBC encourages all Primary Investigators (PIs) to consult with any member of the committee during the planning phases of their IBC protocol The PI must be a salaried UT faculty member OR other salaried contract personnel IMPORTANT: If your IBC will be linked to an animal protocol (IACUC), the IBC protocol must be approved first before the animal protocol will be approved All new protocols must be submitted on the most current template, which can be found at www.utoledo.edu/research/forms www.utoledo.edu/research/forms Protocols must be sent electronically from the PI’s mailbox to Monika DeGregorio (Monika.DeGregorio@utoledo.edu). Please do not send hard copies!Monika.DeGregorio@utoledo.edu IBC meets the 3rd Thursday of each month. PI’s are invited and encouraged to attend the meeting Required training must be completed by the PI and all personnel on the protocol before final approval; otherwise, they cannot begin the proposed studies. Training must be repeated annually. – For BSL1 protocols, Laboratory Safety is required. Training is done through EHRS – For BSL2 protocols, Laboratory Safety & Biosafety training is required. Training is done through EHRS – For BSL3 protocols, Laboratory Safety, Biosafety, and BSL3 training is required, along with mandatory federal training and clearance Last updated 22 Feb. 20166

7. What are the possible outcomes of the IBC review? Approved – IBC Administrator will send a final electronic copy to the PI to be printed twice, signed, and returned to the IACUC office via campus mail or personal drop off. – Committee chair signs the approved protocol, original is returned to the PI, and work can begin. Modifications are required to secure approval – A memo will be emailed to the PI indicating the modifications that need to be performed before the protocol can be approved. – The revised protocol will be re-reviewed via designated member review (typically the Chairman and/or reviewer #1 and/or reviewer #2). – Protocol will be approved after all requested revisions have been made (see above). Deferred or tabled review – If the committee feels that substantial information is lacking and/or insufficient to clearly understand the critical aspects of the protocol, then the protocol will be deferred. – Memo is emailed to the PI describing the issues that need to be changed or clarified. – Because the revised protocol will contain a significant amount of additional information, the committee is likely to require additional modifications that were not part of the initial review. – If deferred, the PI must attend all the follow-up IBC meetings to directly answer any questions the committee may have; however, they will not be able to remain in the room when the committee takes the final discussions/voting. If the PI does not attend, the protocol will not be reviewed. Last updated 22 Feb. 20167

8. What happens after my protocol is approved? A successful IBC Protocol is approved for 5 years, minus one day, from the date of the IBC Chairman’s signature – Every 5 years, resubmission of the protocol is required for a complete review – This resubmitted protocol will contain all amended materials since the last submission – Annual electronic updates are required from PIs regarding whether the protocol remains active; these will be received and completed via email As a courtesy, the IBC office will send out a notice via email or interoffice mail prior to the 5 year expiration date – This will both remind you to resubmit the protocol and provide the deadline for resubmission – If for some reason, the PI has not received this reminder, it is the PI’s responsibility to know his/her expiration date of the protocol and to resubmit in time for review before the termination date BSL1 renewals can be reviewed by the Committee Chairman. The form for BSL1 renewals will be obtained from the IBC administrator BSL2 (or higher) renewals are reviewed by the full IBC committee and must be submitted on form RSP601 Last updated 22 Feb. 20168

9. What if I need to add new materials/procedures to my protocol? Protocols need to be amended for a variety of reasons – Changes in personnel – Addition of new project(s) under current protocol – Changes in containment procedures to a lower biosafety level – Changes to the source of DNA, host or vector – The use of more than 10 liters of material containing rDNA – Changes in the organism studied or increase in biohazard level (mammalian, human or plant) – Changes in location of research – Changes in procedures The PI should complete form RSP605, mail a signed, hard copy to the IBC administrator (Monika DeGregorio MS 1020) – If the changes do not entail a change in BSL level, the Chairman can review and approve the amendment without it being discussed in the full IBC meeting – However, if the amendment requires a change in BSL level, the amendment will need to be discussed in the next IBC meeting Approved changes are recorded in the IBC meeting minutes, and the PI will receive the Chairman-endorsed amendment via campus mail Last updated 22 Feb. 20169

10. What other departments/officials provide lab safety oversight? Members from the Department of Environmental Health and Radiation Safety (EHRS) are responsible for inspecting the labs where research covered by an IBC protocol is performed – Will consult with the PI to ensure that the lab environment and equipment meet the biosafety standards required for the work described in the IBC protocol – Will ensure the PI performs annual certification of Biosafety Cabinets for BSL2 protocols One or more members from the Department of EHRS serve on the IBC to allow timely incorporation of their input – The Institutional Biosafety Officer and the Responsible Official are permanent members of the IBC committee Approval of an IBC protocol is contingent on: – Satisfactory completion of a biohazard lab inspection – Appropriate training of personnel on the protocol – Completing all corrective action items identified by EHRS Last updated 22 Feb. 201610

11. Helpful hints for completing an IBC protocol? There are certain issues in a research protocol that the IBC scrutinizes closely to ensure that research is being performed safely and within the IBC guidelines. These include: Confirmation of biosafety containment level (BSL) needed to complete the work – Thus, it is important to clearly list the microbes and cell lines to be used Through Department of EHRS, assessment of lab space, equipment, and lab practices Through Department of EHRS, confirming that all personnel have completed all necessary laboratory safety and biosafety training Assessment of the risks posed by the work described, including – If viral vectors are being used, ensure they are replication deficient – If infectious materials and/or tissues are being assessed, are the materials being inactivated/killed before taking outside the biological safety cabinet for further analyses? Transport of biological materials between different lab spaces, buildings, or institutions must be clearly defined and performed by trained personnel – EHRS also provides shipping training An IBC protocol will be reviewed more expeditiously if the above issues are clearly explained in the protocol Last updated 22 Feb. 201611

12. Overview for submitting and gaining approval of an IBC protocol Protocol BSLBSL1 BSL2 TBD BSL3 Type of Work or Category NIH Guidelines Section III-F NIH Guidelines Section III-E (transfer synthetic DNA >67% viral genome, transgenic mice) NIH Guidelines Section III-D NIH Guidelines Non-recombinant infectious agents; biological toxins NIH Guidelines Blood-borne pathogens (BBP); human blood, tissues, etc. NIH Guidelines Section III-A & III-B (Transfer antibiotic resistance or toxin genes) NIH Guidelines Section III-C (Transfer of nucleic acids into humans) NIH Guidelines Section III-D; select agents & toxins, non-select agent BSL3 agents ExternalNIH/EHRS BMBL/CDC NIH/OBA CDC InternalIBC/EHRS IBC/IRBIBC/RO Submit What to Whom Protocol to IBC Appendix M, etc. to NIH OBA and IBC/IRB Coordinated by RO. Includes CDC, DOJ, Dean, IBC, DURC Begin Work or Wait for Approval Begin concurrent with submission Wait until IBC approval is issued Wait for NIH & IBC approval Wait for NIH/OBA/RAC, IBC, IRB approval Wait until all aspects of review are complete and RO issues approved Approval CriteriaSatisfactory protocol content; BSL1- appropriate work Satisfactory protocol content, personnel training, lab inspections TBDOBA/RAC outcome; satisfactory Appendix M, etc. Multiple considerations depending on agents used Review ProcessAdministrative review with option of more committee member; no vote Two designated reviewers; full committee vote at meeting IBC submits information from PI/registration to NIH See Appendix M; IBC waits for OBA; IRB waits for IBC Multi-step, external & internal, coordinated by RO Outcome Notification Approval letter issued stating BSL & criteria for protocol or amendment Approval letter issued stating BSL, ABSL, vectors & criteria for protocol or amendment Approval letter issued stating BSL & criteria for protocol or amendment NIH emails outcome to IBC & PI Letter indicating BSL & other requirements, including reporting Different review bodies depending on agent; RO compiles before work can begin Duration of Approval 5 years TBDOpen with annual reports to IRB & OBA 3 years (CDC); 5 year (IBC); annual by RO Amendment Needed? Any non-exempt work or new categories of exempt Any change in systems; work with pathogens, including viral vectors Any changes in viral vectors, genes cloned, organism studied, etc. Any new pathogens, modify pathogens, animal model, etc. TBD Per clinical trial sponsor or DSMB Defined in regulations and EHRS guidance EHRS (Environmental Health & Radiation Safety) IRB (Institutional Review Board) OBA (Office of Biotechnology Activities) RAC (Recombinant DNA Advisory Committee) RO (Responsible Official – University of Toledo) DAMB (Data and Safety Monitoring Board) Last updated 22 Feb. 201612

13. Flow chart for IBC protocol review Last updated 22 Feb. 201613 PI submits protocol IBC staff pre-review registration Are changes needed? IBC staff pre-review protocol IBC staff assign reviewers IBC reviewers consider protocol Are there questions for PI? IBC staff requests changes IBC reviewers submit comments and/or outcome Protocol discussed at IBC meeting Committee votes EHRS inspection complete? Corrective actions completed (PI)? yes no IBC approval PI notified of disapproval PI notified that changes or additional information requested EHRS performs inspection no yes Approve conditionally Table/DeferResearch protocols cannot be performed at this institution

14. Important numbers for IBC-related issues IBC Administrative Assistant: Monika DeGregorio – Monika.Degregorio@utoledo.edu Monika.Degregorio@utoledo.edu – 419-383-4252 IBC Chairman: R. Mark Wooten, Ph.D. – r.mark.wooten@utoledo.edu r.mark.wooten@utoledo.edu EHRA Biosafety Officer: Skylar Rohrs – Skylar.Rohrs@UToledo.Edu Skylar.Rohrs@UToledo.Edu EHRA Director: Heather Lorenz – Heather.Lorenz@utoledo.eduHeather.Lorenz@utoledo.edu Website: https://www.utoledo.edu/research/RC/biosafety.htmlhttps://www.utoledo.edu/research/RC/biosafety.html Last updated 22 Feb. 201614