Registering Research with the Institutional Biological Safety

Committee (IBC)

A Guide to the Biohazard and Recombinant DNA Registration Process at Princeton University

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.

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.

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.

What material should be registered?

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

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.

Completing the Registration Form

If your research is exempt from the Guidelines, select the category that best describes your exempt research .

•Breeding of almost* all transgenic rodents that require BSL-1 housing is exempt under section III-F-6

*ExceptionsRodents 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.

More exemptions… 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).

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

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

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.

Completing the Registration Form

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

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.

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.

Completing the Registration Form

If you work with more than one infectious agent, click on this button to repeat the questions in section 4.

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.

Completing the Registration Form

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

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.

Completing the Registration Form

Risk AssessmentNIH 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.

Risk Group 1 Risk Group 2 Risk Group 3 Risk Group 4

Agents that are not associated with disease in healthy adult humans

Agents are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available

Agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available

Agents that are likely to cause serious or lethal human disease for which preventive therapeutic interventions are usually not available

All serotypes of adeno-associated virus1, Bacillus subtilis, Escherichia coli K-122

Listeria, Salmonella typhimurium, Staphylococcus aureus, E. coli 3, human adenoviruses, Herpes simplex types 1 and 2

There are no facilities available for research with Risk Group 3

or 4 agents at Princeton University.

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

Principal Investigator’s Risk Assessment

After you have determined the Risk Group of the agent:

Evaluate agent factorsvirulence, pathogenicity, infectious dose, environmental stability, route of spread, communicability, quantity, availability of vaccine or treatment

Evaluate gene product effectstoxicity, 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.

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: 609 258-5294Email: jw6@princeton.edu