1. Introduction to the MUSC Institutional Biosafety Committee (IBC) Registration Process Daniel Eisenman, PhD MUSC Biosafety Officer eisenman@musc.edu 843-792-4304

2. Requires: Institutions receiving NIH funding to have Institutional Biosafety Committees (IBC) Registration and IBC review of rDNA Research Ensure Risk Assessments are performed Implementation of Containment and Safety Practices Outlined in: Biosafety in Microbiological and Biomedical Laboratories (BMBL) NIH Guidelines for Research Involving Recombinant DNA

3. Origins of NIH Guidelines for Research Involving Recombinant DNA Framework created at the 1976 Asilomar academic conference by researchers in response to public fears over: gene therapy creation of “super bugs” (e.g. virulent antibiotic resistant microorganisms) The guidelines were later adopted and implemented by the NIH. April 18, 1977

4. Overview of the MUSC IBC Registration Process Online submission via the ERMA System http://erma.musc.edu/

5. Overview of the MUSC IBC Registration Process Online submission via the ERMA System http://erma.musc.edu/ Initial Review by IBC Members Feedback Provided to Investigators Opportunity to Revise Application Prior to the IBC Meeting IBC Meets to Review and Discuss Applications IBC Approval and Laboratory Inspection

6. Submission Deadlines and Meeting Dates www.musc.edu/biosafety/IBC

7. Guidance Documents and Assistance Instructions https://erma.musc.edu/ibc_office/GenIntruct.html Biosafety Officer’s Webpage www.musc.edu/biosafety Links to a Frequently Asked Questions page has been embedded in the IBC Form. Additional Assistance Daniel Eisenman, PhD Biosafety Officer eisenman@musc.edu Yashmin Karten, PhD IBC Administrator karteny@musc.edu IBC Website http://research.musc.edu/ori/ibc/home.htm

8. Biosafety Officer’s Webpage www.musc.edu/biosafety Links to FAQ Page embedded in the IBC Form Guidance Documents and Assistance

9. Design and Structure of the IBC Forms Modular Forms with 7 Sections Four Required Sections Section 1: PI Information and Personnel Listing Section 2: Locations (laboratories, culture rooms, etc.) Section 3: Description of Research and Funding Information Section 7: PI’s Acknowledgement of Responsibilities

10. Design and Structure of the IBC Forms Three Sections To Be Used As Needed Section 4: Recombinant DNA Section 5: Microbes Section 6: Biological Toxins

11. Section 4: rDNA Disclose Genes to be expressed Vectors (plasmids, viruses, etc.) Investigators should be aware of potential risks associated with: Aberrant expression of genes in humans Consequences of Infection with recombinant organisms e.g. E. coli and viral vectors Designed to assess potential risks associated with rDNA.

12. Section 5: Microbes Includes cloning strains of E. coli and Saccharomyces cerevisiae www.musc.edu/biosafety/E%20coli Viral Vectors Must Also Be Disclosed As Microbes. www.musc.edu/biosafety/IBC Designed to assess potential risks associated with microbes

13. Section 6: Biological Toxins Biological toxins must be registered with the IBC. Toxins of greatest concern are Select Agent Toxins which are regulated by the CDC when possessed in quantities exceeding the permissible amounts listed below.

14. Risk Assessment 101 The Investigator must be able to identify the risks associated with their experimental design. The risks associated with genes of interest and vectors must be disclosed.

15. Section 4e: Registering genes to be expressed The IBC places Great emphasis On identifying gene Hazards.

16. Determining Risks Associated with Genes Hazard: Elevated expression of GATA6 may lead to oncogenesis.

17. Retrovirus Lentivirus Adenovirus Adeno- Associated virus Viruses are Diverse! Several animal virus families possessing varying properties, uses and risks.

18. Virus Target Cell Infected target cell containing the gene of interest Cell’s DNA Viral RNA Gene of Interest Example Risk Assessment Risks Associated with Retroviral Vectors: Viral Transduction Individuals infected with the viral vector may express the insert gene at the site of infection. Oncogenes, Immune Modulators and Toxins pose the greatest risk.

19. Example Risk Assessment Risks Associated with Retroviruses: Insertional Mutagenesis Virus Target Cell Host Cell DNA Viral RNA Gene of Interest Proto-Oncogene Oncogene Random integration of viral genome may disrupt endogenous host genes. Of special concern Is disruption of proto-oncogenes, which can lead to increased cancer risk.

20. Fever / flu-like symptoms Possible inflammation of infected tissues Random integration of viral genome into host genome can result in insertional mutagenesis and oncogenesis Expression of insert genes in infected tissues may pose additional risk depending on the gene’s function. Likely Consequences of Lab Acquired Infections with Retro/Lentiviral Vectors

21. Risk Assessment 101: Containment and Safety Practices Experimental Procedures Use of Sharps Use of Animals Potential Creation of Aerosols Procedures on Bench Tops vs Biosafety Cabinets Additional Consideration for Containment, personal protective equipment (PPE) and Safety Practices May be Required After Assessing: Microbes Host Range (Infectious to human?) Virulence Concentration / Viral Titer Large Volumes

22. Approval Pending A Satisfactorily Completed Laboratory Inspection New applications or amendments covering new Investigators, locations or organisms will require a lab inspection. Contact the Biosafety Officer to schedule inspections. Daniel Eisenman, PhD Biosafety Officer eisenman@musc.edu 843-792-4304

23. Laboratory Inspections Online Guidance: www.musc.edu/biosafety/BSL2 Inspections Ensure Compliance with the Containment and Safety Practices Detailed in the BMBL, the CDC’s biosafety guidelines. Pre-inspection Walk- Throughs Can be Scheduled to provide guidance. Most Deficiencies Are Corrected During or Shortly After Inspection.

24. Laboratory Inspections: Most Common Deficiencies Signed Lab Safety Protocol Not Available At Inspection Template Safety Protocols Available Online: www.musc.edu/biosafety/SafetyProtocol Expired Biosafety Cabinet Certifications Contact the Biosafety Officer to arrange certification.

25. Regulatory Changes Synthetic Oligonucleotides 9 AUGUST 2002 VOL 297 SCIENCE Dual Use Research http://news.sciencemag.org/scienceinsider/2012/03/us-requires-new-dual-use-biologi.html ©2006 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 7 | SPECIAL ISSUE | 2006

26. Questions? Daniel Eisenman, PhD MUSC Biosafety Officer eisenman@musc.edu 843-792-4304