1. INSTITUTIONAL REVIEW OF BIOSAFETY RESEARCH Review of Institutional Biosafety Committee Application Form Robert J. Hashimoto The University of Kentucky November 2002

2. INTRODUCTION The use of biological materials is closely regulated by both environmental and administrative regulations. –The Institutional Biosafety Committee (IBC) and Biosafety Officer are tasked with ensuring that the institution adheres to environmental guidelines and meets the requirements of the National Institutes of Health Recombinant DNA Guidelines. –The Office of Research Administration/the Sponsored Projects Office/Dean of Research may also play a role in administrative compliance.

3. RESPONSIBILITIES OF THE BIOLOGICAL SAFETY OFFICER/EHS The functions of the Biological Safety Officer include, but are not limited to the following: Inspect laboratory facilities for suitability of biological work Respond to biosafety emergencies and other contamination incidents Provide consultation to campus employees regarding the safe use of biological materials Review grants for IBC review and approval

4. RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR (P.I.) Some of the administrative functions of the Principal Investigator include the following: Request approval for experiments involving the use of biohazardous agents or non-exempt recombinant DNA molecules from the IBC prior to the initiation of work Ensure that all employees who are working with blood, Hepatitis B Virus or other agents receive appropriate medical surveillance

5. OTHER ADMINISTRATIVE DUTIES OF THE PRINCIPAL INVESTIGATOR Notify the IBC whenever: - the lab is being closed down - the scope of work changes - the P.I. is leaving the institution - the lab is being relocated - the P.I. plans to add additional lab rooms or personnel to the current IBC approval

6. PRINCIPAL INVESTIGATOR, cont. Provide training appropriate for the hazards associated with the biological work performed. (The Biosafety Officer will also provide training upon request.) Ensure that the front door of the lab is labeled with a biohazard sign for Biosafety Level 2 or 3 work. Ensure that all biosafety cabinets are certified on an annual basis or sooner, if moved.

7. RESPONSIBILITES OF ADMINISTRATORS The Administrative Managers: are the key individuals who coordinate administrative activities between the IBC and Biosafety Officer and the P.I. Some duties include: Retain applications on file on behalf of the department and the investigator Prepare and review grants with biohazardous agents and recombinant DNA use

8. REVIEW OF AN IBC APPLICATION FORM

9. THE IBC APPLICATION FORM The IBC application form is designed for the Principal Investigator to describe his or her work with biological agents to the IBC.

10. IBC APPLICATION FORM, cont. The criteria for completing an application include: Any work which involves research with infectious agents and non-exempt recombinant DNA molecules. The clinical diagnoses of patient care or human subjects specimens is considered research if the diagnostic procedures exceed the identification of pathogenic organisms. Any work which involves biological specimens, which depending on the procedure, can have consequences if not properly handled.

11. IBC APPLICATION FORM, cont. The application must be: –typed –completed in full –submitted with an adequate number of copies The IBC will look at the risk determination portion of the form in great detail. It is essential that the P.I. describes: –the biological agents used –the potential health effects if the biohazardous agents are released to the environment

12. How to fill out Certification Statement The PI must read and sign the statement which verifies that the PI: Provides training Provides personal protective equipment Offers vaccinations, medical surveillance Is familiar with emergency procedures

13. How to fill out Title The title of the project is often different from the grant title, especially if multiple grants are being submitted to different funding sources. The PI must be certain that the research project title is used consistently for all IBC correspondence; different applications to different institutional committees may result in confusion when it is time to renew the IBC application form.

14. How to fill out Biosafety Level The biosafety level of the research is primarily based on the organism used. The PI can refer to the CDC guideline, Biosafety in Microbiological and Biomedical Laboratories to make the initial estimate for the biosafety level. The IBC will make the final determination of biosafety level based on the organism used and the experimental procedures.

15. How to fill out Other Institutional Reviews Some experiments require other institutional committee approvals if animals, radioactive materials or human subjects are used. If other approvals are needed in conjunction with the experiment, the PI must indicate the status of these approvals. The PI must obtain approvals from other institutional committees prior to the IBC granting final approval.

16. How to fill out Personnel The PI should list all personnel who will be physically handling the biological agents or recombinant DNA molecules. The PI must also indicate safety training and vaccination status, as necessary. The PI must add a separate page if more than six people will be working on the project and all relevant information must be completed.

17. How to fill out Agent Location The PI must f ill out the location of all the rooms that shall be used for agent work. Tissue culture, equipment and other shared rooms should be identified to ensure that biohazard labels are placed to indicate agent usage in these shared rooms. The PI should estimate the biosafety level of the work in each room-the IBC will review this estimate at the convened meeting.

18. How to fill out Containment Physical containment equipment refers to the tissue culture hoods/biosafety cabinets that will be used to perform potential aerosol-generating procedures. After providing the location of the biosafety cabinet, the PI should write down the model of the biosafety cabinet, ID number and date of certification. This will be verified by the Biosafety Officer prior to the IBC meeting.

19. How to fill out Project Description The PI must compose a synopsis of the proposed experiment IN LAY TERMS. This project summary must include the following: 1. Purpose of the experiment 2. Risk for infection/hazard assessment 3. Procedures to contain agents 4. Special considerations for handling (e.g. vaccinations, personal protective clothing use)

20. How to fill out Project Description Checklists and outlines are available for use in preparing the summary of work. If both biohazardous agents and recombinant DNA molecules are used in an experiment, then the work practices for safe use and handling need not be repeated. The summary should be no more than one page. Articles and abstracts may be attached to the form if they may provide clarification for the proposed work.

21. How to fill out Project Description The checklists are designed to ensure that the PI is aware of the issues that the IBC is looking for. Essential information can be disseminated to the IBC by the PI checking a box, and elaborating on any affirmative answers in the scope of work statement.

22. How to fill out Project Description In the Scope of Work narrative, the IBC would particularly like to know the following information: What is the purpose of the experiment? Where were the agents obtained? Will large volumes of culture or high concentrations of agents be used? Will sharp objects or aerosol-generating procedures be used? Are there special containment considerations?

23. How to fill out Project Description How will agents be transported outside the building? Are toxic recombinant molecules produced? Is the lab space shared with non-agent users? Is a biosafety cabinet NOT AVAILABLE? Will any work be performed off campus? Are the special considerations for medical waste disposal?

24. THE EXPERIMENTS WHICH DO NOT REQUIRE IBC APPROVAL The following experiments do not require IBC approval or review: Any experiment involving the exclusive use of: –Class 1 agents –Exempt Recombinant DNA Molecules (Section III-F) –Experiments involving the use of human or animal clinical specimens or cell lines which are not known to be infectious

25. RECOMBINANT DNA CONSIDERATIONS do not have to be registered with the IBC. Experiments involving the use of Exempt Recombinant DNA molecules do not have to be registered with the IBC. The P.I. will not have to apply to the IBC if: –the Recombinant DNA molecules are exempt under the NIH Guidelines and –do not involve Class 2 biological agents as defined by the CDC

26. DEFINITION OF EXEMPT RECOMBINANT DNA The use of an exempt recombinant DNA molecule does not require IBC review and approval, according to the NIH Guidelines. Experiments involving these exempt recombinant DNA molecules are described in Section III-F of the NIH Guidelines.

27. NIH RECOMBINANT DNA GUIDELINES The Federal Register, April 2002 –describe the guidelines for research involving Recombinant DNA molecules –a copy is available from the NIH, www.nih.gov Those experiments involving recombinant DNA which do require IBC review and approval –usually involve the use of pathogenic organisms or –involve introduction recombinant DNA molecules to human or animal subjects

28. RECOMBINANT DNA SECTION OF THE APPLICATION The Recombinant DNA information on the IBC application form must include the following information: Host/Vector information, e.g.; E-coli K12, pBR322 DNA source Name of genes cloned Acknowledgment of human blood used Location of facilities

29. How to fill out RECOMBINANT DNA WORKSHEET The Recombinant DNA questionnaire summarizes every category of experiment involving the use of recombinant DNA molecules. It is based on Section III, parts A through F of the NIH Guidelines for the Use of Recombinant Molecules. The PI must complete this worksheet if recombinant DNA molecules are being used in the experiment.

30. How to fill out RECOMBINANT DNA WORKSHEET The Recombinant DNA questionnaire lists several categories of experiments that sound similar. Some observations: 1. Any use of human pathogens/recombinant DNA molecules as part of a host-vector system is a Class III-D experiment. 2. Any use of recombinant DNA molecules and transgenic animals is a Class III-D-4 or a Class E-5 experiment

31. How to fill out RECOMBINANT DNA WORKSHEET Any introduction of recombinant DNA molecules to human subjects is a Class III-C-1 experiment. (Note that this experiment requires both IBC and IRB approval. The PI must also complete the NIH Guidelines for the Use of Recombinant DNA Molecules, Appendix M for submission to the IBC along with the application form.)

32. OTHER CONSIDERATIONS then the Biohazardous Agent section of the IBC Application form must be completed concurrently with the Recombinant DNA Worksheet portion of the form. If human blood, tissue or other specimens which are known to be infected with human pathogens, such as BL 2 or BL 3 microorganisms, are used in the recombinant DNA experiments, then the Biohazardous Agent section of the IBC Application form must be completed concurrently with the Recombinant DNA Worksheet portion of the form.

33. BIOSAFETY INSPECTIONS Any application form submitted to the IBC will require a biosafety inspection of the facilities by the Biological Safety Officer. Inspections will be conducted on an annual basis thereafter.

34. NO APPLICATION NEEDED The P.I. does not have to complete an application to the IBC if the experiment:The P.I. does not have to complete an application to the IBC if the experiment: –is identical to an IBC experiment approved or renewed within the past year –is exempt under NIH Recombinant DNA Guidelines –does not include the use of class 2 or 3 agents

35. APPLICATION TO THE IBC FINAL THOUGHT A rule of thumb: If the biological organism used in the experiment can cause an infection in a healthy human, animal, or plant, then it should be reviewed by the IBC.

36. CONCLUSION The IBC and EHS serve in the process of monitoring biological research in your institution. It is critical that the IBC work with the University Research Administration Departments and other institutional committees. The application form must be completely filled out. The PI must be informed if the form is not adequate and the form should be returned.