Registering Research with the Institutional Biological Safety Committee (IBC)

1. Registering Research with the Institutional Biological Safety Committee (IBC) A Guide to the Biohazard and Recombinant DNA Registration Process at Princeton University

2. This training is designed to familiarize Principal Investigators with the revised Biohazard/recombinant DNA (rDNA)Form, formerly the Memorandum of Understanding and Agreement (MUA). The Form has been significantly revised to respond to feedback received from the NIH Office of Biotechnology Activities, the government agency that administers the NIH Guidelines for Research Involving Recombinant DNA Molecules.

3. What material should be registered? • Use the form to register work with the following materials: • rDNA that is exempt from the Guidelines • rDNA that is not exempt from the Guidelines • The IBC Chair and the BSO will review this research , issue approval and a containment level. The IBC does not review exempt research. Non-exempt research must be reviewed and approved by the IBC.

4. What material should be registered? • The following materials also need to be registered with the IBC: • biological material from human and non-human primates • microorganisms and viruses pathogenic to humans, plants or animals, toxins of biological origin Can be approved by the Biological Safety Officer Non-recombinant biosafety level 2 organisms and viruses can be approved by the BSO and the IBC Chair. Either may request a full Committee review. All biosafety level 3 research, including work with select agents and toxins must be approved by the URB.

5. Completing the Registration Form • Check the category (ies) that apply to your research. Only those questions pertinent to the research categories checked will appear on the form.

6. If your research is exempt from the Guidelines, select the category that best describes your exempt research . Completing the Registration Form • The IBC Chair and Biosafety Officer will confirm the containment level and issue approval. • The full IBC Committee does not review exempt recombinant or synthetic nucleic acid molecule research.

7. More exemptions… Completing the Registration Form • Breeding of almost* all transgenic rodents that require BSL-1 housing is exempt under section III-F-6 • *Exceptions • Rodents that contain a transgene encoding >50% of an exogenous eukaryotic virus. • Transgenic rodents in which the transgene is under control of a gammaretroviral promoter. • Any breeding experiments that require BSL-2 conditions.

8. Completing the Registration Form • Research that falls under Section III-D must be reviewed and approved by the IBC before initiation. • Examples of research in this category: • using lentiviral or adenoviral vectors • gene inserts from pathogenic microorganisms • administering rDNA to animals, except for creating transgenic rodents(see Section III-E-3).

9. Completing the Registration Form • Section III-E covers experiments in which all components are derived from non-pathogenic prokaryotes and non-pathogenic lower eukaryotes and may be conducted at Biosafety Level 1 containment. If BSL-2/ABSL-2 containment is required, the research is not covered by Section III-E. • Examples: • rDNA molecules of eukaryotic viruses that contain no more than 2/3 of the viral genome: • in tissue culture only and BSL-1 containment • must demonstrate the lack of a helper virus for certain families of defective viruses being used • Creating transgenic rodents requiring BSL-1 containment

10. Completing the Registration Form • Experiments that require IBC approval, Recombinant Advisory Committee and NIH Director approval prior to initiation: • deliberate transfer of a resistance trait that could compromise the use of a clinically significant drug to treat infections • formation of rDNA containing genes for toxin molecules that are lethal to vertebrates: • toxins that have an LD50 of less than 100ng/kg body weight, such as botulinum toxin, tetanus toxin, diptheria toxin, Shigella dysenteriae neuorotoxin

11. Completing the Registration Form If your work with rDNA is not exempt and doesn’t fall into categories III A, B, D or E, review Section III of the Guidelines, provide a brief description and the appropriate Guidelines reference.

12. Completing the Registration Form For each non-exempt host-vector system used in your research, answer the questions in Section 3.

13. Completing the Registration Form Additional questions will appear under each vector you select when completing Section 3. The information you provide allows the IBC to conduct a thorough risk assessment. For example, if your research involves use of an adenovirus vector, you’ll be prompted to provide additional details on the vector.

14. Completing the Registration Form For each agent that could potentially cause disease in humans, fill out Section 4, designed to collect information that will assist the IBC with assigning containment levels for both recombinant and non-recombinant infectious agents. If you work with more than one infectious agent, click on this button to repeat the questions in section 4.

15. Completing the Registration Form Complete Section 5 to register human and non-human primate blood and body fluids, primary cells and established cell lines, except as noted below, with the IBC. Established human cell lines that are characterized to be free of contamination from human hepatitis viruses, human immunodeficiency viruses and other recognized bloodborne pathogens are not covered by OSHA’s Bloodborne Pathogen Standard and do not have to be registered. Documentation that the cell lines are free of bloodborne pathogens should be available for review by the Biosafety Officer and regulatory agencies, such as OSHA.

16. Completing the Registration Form Use Section 6 to register research with toxins of biological origin, such as botulinum toxin, tetrodotoxin or conotoxin.

17. Completing the Registration Form Section 7 should be completed if you are working with any organism or virus, including recombinant materials, that could potentially infect humans.

18. Risk Assessment NIH Guidelines require that the Investigator make an initial assessment of risk based on the Risk Group (RG) of an agent, using information provided in Appendix B of the Guidelines. Examples 1 if transgene does not encode either a potentially tumorigenic gene product or a toxin molecule and virus is produced in absence of a helper virus 2 if it does not possess a complete lipopolysaccharide and does not carry any active virulence factor or colonization factors and does not carry any genes encoding these factors. 3 enteropathgenic, enterotoxigenic, enteroinvasive and strains bearing K1 antigen, including E. coli O157:H7

19. Principal Investigator’s Risk Assessment After you have determined the Risk Group of the agent: Evaluate agent factors virulence, pathogenicity, infectious dose, environmental stability, route of spread, communicability, quantity, availability of vaccine or treatment Evaluate gene product effects toxicity, physiological activity and allergenicity Evaluate how the agent will be used: animal experiments, large production (>10 liters) Determine the biosafety level required based on the above information.

20. Additional Resources: If you experience technical difficulties when completing the form, contact: Research Integrity and Assurance Email: jpass@princeton.edu If you have questions about biosafety issues, contact: Biosafety Officer Phone: 609 258-5294 Email: jw6@princeton.edu